PT2461767E - Silicone hydrogel lenses with water-rich surfaces - Google Patents

Abstract

Hydrated silicone hydrogel contact lens having a layered structural configuration: a low water content silicone hydrogel core (or bulk material) completely covered with a layer of a water-rich (e.g., a water content greater than 80%), hydrogel totally or substantially free of silicone. A hydrated silicone hydrogel contact lens of the invention possesses high oxygen permeability for maintaining the corneal health and a soft, water-rich, lubricious surface for wearing comfort.

Description

ΡΕ2461767 1

DESCRIPTION

&quot; SILICON HYDROGEL LENSES WITH RICH SURFACES IN WATER &quot; The present invention relates generally to an ophthalmic device, in particular a silicone hydrogel contact lens having a structural configuration creating a water content gradient and comprising: a silicone hydrogel mass material having a water content ( designated as WCSiHy) from about 10% to about 70% by weight and an outer skin layer having a thickness of about 0.1 to about 20 μm and completely covering the mass material in silicone hydrogel and effecting in a substantially silicone-free or substantially silicone-free hydrogel material, characterized by a ratio of at least about 10% if WCsiHy <45% or by a water-swelling ratio of at least about of [120 · WCSiHy / (1 · WCsiHy)]% is WCsiHy> 45%, as measured by AFM with a cut of the silicone hydrogel contact lens in a fully hydrated state.

BACKGROUND

Silicone hydrogel contact lenses (SiHy) are widely used to correct many different types of vision impairments. They are made of a 2 ΡΕ2461767 hydrated cross-linked polymeric material which contains, in equilibrium, silicone and a certain amount of water within the polymer matrix of the lens. According to the FDA classification for contact lenses, hydrogel contact lenses are generally classified into two main categories: low water contact lenses (containing less than 50% water) and high contact lenses in water (containing more than 50% water). For SiHy contact lenses, a high oxygen permeability, which is required for a contact lens to have minimal adverse effects on corneal health, is achieved by the incorporation of silicone, by increasing the water content, in the crosslinked polymeric material. As a result, unlike conventional hydrogel contact lenses, SiHi contact lenses may have a reduced water content while still having relatively high oxygen permeability (Dk), for example, Focus® Night &amp; Day® from CIBA Vision Corporation (ca. 23.5% H2O and Dk-140 Barrers); Air Optix® from CIBA Vision Corporation (ca. 33% H20 and Dk-110 Barrers); PureVision® from Bausch &amp; Lomb (ca 36% H 2 O and Dk-100 Barrers); Acuvue® Oasys® from Johnson &amp;

Johnson (ca. 38% H2O and Dk-105 Barrers); Acuvue® Advance® from Johnson &amp; Johnson (ca. 47% H2O and Dk-65 Barrers); Acuvue® TruEye ™ from Johnson &amp; Johnson (ca. 46% Η 20 and Dk-100 Barrers); and Menicon ™ Award (ca. 40% Η20 and Dk-129

Barrers). Water in a SiHy contact lens can provide the desirable softness that allows a SiHy lens to be used for long enough periods and confer benefits to patients including adequate initial comfort (i.e., immediately after lens insertion), a relatively short of the adaptation time required for a patient to become habituated thereto and / or appropriate suitability. A higher water content would be desirable to produce SiHy contact lenses with biocompatibility and comfort. But, there is a limit to the amount of water (believed to be 80%) that a SiHy contact lens can contain while still possessing sufficient mechanical strength and stiffness required to a contact lens, such as hydrogel contact lenses conventional. In addition, a high water content could also have undesirable consequences. For example, the oxygen permeability of a SiHy contact lens could be compromised by the increase in water content. In addition, a higher water content in a SiHy lens could result in increased ocular dehydration and hence discomfort induced in dehydration, because a SiHy contact lens with a high water content could weaken the limited supply of tears (water ) of the eye. It is believed that ocular dehydration can be derived from evaporation (ie, loss of water) on the anterior surface of the contact lens and this loss of water is mainly controlled by the diffusion of water through a lens from the posterior surface to the anterior surface and that the rate of diffusion is quite proportional to the water content of the mass matter of the lens in equilibrium (L. Jones et al., Contact Lens &amp; Anterior Eye 25 (2002) 147-156, herein incorporated by reference. totality). Incorporation of silicone into a contact lens material also has undesirable effects on the biocompatibility of the contact lens because the silicone is hydrophobic and has a high tendency to migrate upward from the surface of the lens exposed to air. As a result a SiHy contact lens will generally require a surface modification process to eliminate or minimize exposure of the contact lens silicone and to maintain a hydrophilic surface, including, for example, various plasma treatments (e.g., Focus® Night Day & Air Optix® from CIBA Vision Corporation; Bausch & Lomb's PureVision® and Menicon's "PremiO ™"); internal wetting agents physically and / or chemically embedded in the SiHy polymer matrix (for example, Acuvue® Oasys®, Acuvue® Advance® and Acuvue® TruEye ™ from Johnson &Johnson; Biofinity® and Avaira ™ from CooperVision). While surface modification techniques used in the production of commercial SiHy lenses can provide fresh (unused) SiHy lenses with suitably hydrophilic surfaces, a SiHy lens used in the eye may have dry spots and / or hydrophobic surface areas created either due to exposure to air, eyelid cutoff forces, silicone migration and / or partial failure to prevent exposure of the silicone. Such dry patches and / or hydrophobic surface areas are non-moist and likely to absorb lipids or proteins from the ocular environment and may adhere to the eye causing discomfort to the patient. US20090200692 discloses a method for the manufacture of a silicone hydrogel contact lens having a sandwich structure which is composed of a body of silicone hydrogel material completely coated with a hydrophilic biomedical material. The method disclosed in US20090200692 comprises: regularly coating a film of a hydrophilic biomedical material in a thickness of about 0.1 to 10 microns in the male and female halves of a casting mold; semi-curing the film of the hydrophilic biomedical matter in the male and female halves of the mold; fill the female half of the mold with the semi-cured film of hydrophilic biomedical matter overhead; pressing the half of the male mold with the film of hydrophilic biomedical matter over the female mold containing the material in silicone hydrogel; using ultraviolet radiation and / or heat source to bind / cure the semi-cured films of the hydrophilic biomedical matter onto the respective surfaces of the male and female halves and the silicone hydrogel matter contained in the mold to form a lens of having a sandwich structure.

Therefore, there is still a need for SiHy contact lenses with hydrophilic surfaces that have a persistent hydrophilicity, moistening and lubrication that can be maintained in the eye throughout the day. 6 ΡΕ2461767

SUMMARY OF THE INVENTION The present invention may satisfy the needs for SiHy contact lenses having hydrophilic surfaces which have a persistent surface hydrophilicity, surface wetting and surface lubrication throughout the day.

In one aspect, the invention provides a silicone hydrogel hydrated contact lens comprising: an anterior (convex) surface and a posterior (concave) rear surface; and a layered structural configuration from the front surface to the back surface, wherein the layered structural configuration includes a front outer hydrogel layer, an inner layer on a silicone hydrogel material, and a rear outer hydrogel layer, wherein matter in silicone hydrogel has an oxygen permeability (Dk) of at least about 50, preferably at least 60, more preferably at least about 70, still more preferably at least about 90 barrers, most preferably at least about 110 i Barrers, and a first water content (designated as WCsiHy) of from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, still more preferably from about 15% to about 55%, most preferably from about 15% to about 50% by weight, wherein the anterior and posterior exterior hydrogel layers are substantially uniform in thickness and are fused to the peripheral edge of the contact lens to completely enclose the inner layer of silicone hydrogel material wherein the outer anterior and posterior hydrogel layers independent of each other have a second water content higher than WCSiHy, as characterized either by having a water volume increase ratio of at least about [120 - WCSiHy / (1 - WCsiHy) 1% preferably [130 - WCSiHy / (1 - WCSiHy)]%, more preferably [140 · WCSiHy / (1 · WCsiHy)]%, even more preferably [150 · WCsiHy / (1-WCsiHy)]% if WC &gt; 45%, wherein the thickness of each of the outer anterior and posterior hydrogel layers is from about 0.1 Âμm to about 20 Âμm, preferably from about 0.25 Âμm to about 15 Âμm, more preferably from about 0.5 to about 12.5 Âμm, even more preferably from about 1 Âμm to about 10 Âμm (as measured by atomic force microscopy through a cut from the posterior surface to the anterior surface of the contact lens in silicone hydrogel in a fully hydrated state).

In another aspect, the invention produces a silicone hydrogel hydrated contact lens. A silicone hydrogel hydride contact lens of the invention comprises: a silicone hydrogel material having mass matter, an anterior surface and a posterior opposing surface; wherein the contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, plus ΡΕ2461767 preferably at least about 80, still more preferably at least about 110 barrers / mm, and a module profile which comprises, along the shorter line between the anterior and posterior surfaces on the surface of a cut of the contact lens, an anterior outer zone including and close to the anterior surface, an inner zone including and around the center of the shorter line, and a rear outer zone including and near the rear surface, wherein the front outer zone has a middle anterior surface modulus (designated as SMAnt) while the posterior outer zone has an average posterior surface module (designated as SMPost ), wherein the inner zone has an average inner surface modulus (designated by

Sm

( € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒInmultiplex, wherein at least one of SM, ex. about 30%, still more preferably at least about 35%, most preferably at least about 40%.

In yet another aspect, the invention produces a silicone hydrogel hydrated contact lens. A silicone hydrogel hydride contact lens of the invention comprises: a silicone hydrogel material having mass matter, an anterior surface and an opposing posterior surface 9A; wherein the contact lens has (1) an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, still more preferably at least about 110 barrers / mm and (2) a surface lubrication characterized by having a critical coefficient of friction (referred to as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and back surfaces have a reduced surface concentration of negatively charged groups including carboxylic acid groups as characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, still more preferably at most about 90, most preferably at most about 60 particles positively charged in a positively charged particulate adherence test.

These and other aspects of the invention including various preferred embodiments in any combination will become apparent from the following description of preferred embodiments.

Figure 1 schematically shows a cross-sectional view of the structural configuration of a SiHy contact lens according to a preferred embodiment of the invention. Figure 2 schematically illustrates a cross-sectional view of the structural configuration of a SiHy contact lens in accordance with another preferred embodiment of the invention. Figure 3 shows the fluorescence intensity profiles through the cuts of a SiHy contact lens on a laser confocal fluorescence microscopy. Figure 4 shows SEM (Electron Scanning Electron Microscopy) images of a SiHy contact lens of the invention in a lyophilized state. Figure 5 schematically illustrates the assembly of the slant method according to a preferred embodiment. Figure 6 shows microscopic optical images of the contact lenses having different overcoats after being immersed in a dispersion of positively charged particles (DOWEX ™ 1x4 resins of 20-50 mesh). Figure 7 illustrates schematically how to mount a cut-away piece of a SiHy contact lens of the invention vertically in a metal clip for AFM testing. Figure 8 shows the AFM (atomic force microscopy) image of a cut portion of a SiHy contact lens in a fully hydrated state (in phosphate buffered saline, pH 7.3) according to preferred embodiment of the invention. Figure 9 shows a sectional surface module profile of a SiHy contact lens of the invention in a fully hydrated state (in phosphate buffered saline, pH-7.3) along two shorter lines between the anterior and posterior surfaces on the surface of a cut of a SiHy contact lens, in accordance with a preferred embodiment of the invention as approximately represented by the deflection markings of the arm as a function of distance.

DETAILED DESCRIPTION OF MODELS FOR CARRYING OUT THE INVENTION

Reference will now be made in detail to the embodiments of the invention. Other objects, features and aspects of the present invention are disclosed in, or are obvious from, the following detailed description. It should be understood by one of ordinary skill in the art that the present text is only a description of exemplary embodiments and should not be construed as limiting the broader aspects of the present invention. 12 ΡΕ2461767

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this invention pertains. Generally, the nomenclature used herein and the laboratory processes are well known and commonly used in the art. Conventional methods are used for these processes, such as those which are produced in the art and various general references. When a term is given in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are those well known and commonly used in the art.

As used in this application, the term &quot; silicone hydrogel contact lens &quot; refers to a contact lens comprising a silicone hydrogel material.

As used in this application, the term &quot; hydrogel &quot; or &quot; hydrogel matter &quot; refers to a crosslinked polymeric material which is not water soluble and may contain at least 10% by weight water in its polymer matrix when fully hydrated.

As used in this application, the term &quot; non-silicone hydrogel &quot; refers to a hydrogel which, in theory, is free of silicone. the term

As used in this application 13 ΡΕ2461767 &quot; silicone hydrogel &quot; refers to a silicone containing hydrogel. A silicone hydrogel is typically obtained by copolymerizing a polymerizable composition comprising at least one silicone-containing vinyl monomer or at least one silicone-containing vinyl macromer or at least one silicone-containing prepolymer and having ethylenically unsaturated groups.

As used in this application, the term &quot; vinyl monomer &quot; refers to a compound having a single ethylenically unsaturated group and may be actinically or thermally polymerized.

As used in this application, the term &quot; olefinically unsaturated group &quot; or &quot; ethylenically unsaturated group &quot; is used herein in a broad sense and is intended to encompass any groups containing at least one &gt; C = C &lt; group. Exemplary ethylenically unsaturated groups include unlimited (meth) acroyl (ι c

It-ore

HI! C-ΡΕ246176714), allyl, vinyl

Styrenyl, or other groups containing C = C.

As used in this application, the term &quot; (meth) acrylamide &quot; refers to mectacrylamide and / or acrylamide.

As used in this application, the term &quot; (meth) acrylate &quot; refers to methacrylate and / or acrylate.

As used in this application, the term &quot; hydrophilic vinyl monomer &quot; refers to a vinyl monomer which as homopolymer typically produces a polymer which is water soluble or can absorb at least 10 weight percent water.

As used in this application, the term &quot; hydrophobic vinyl monomer &quot; refers to vinyl monomer which, as homopolymer, typically produces a polymer which is insoluble in water and can absorb less than 10 weight percent water.

As used in this application, the term &quot; macromer &quot; or &quot; prepolymer &quot; refers to a medium and high molecular weight compound or polymer containing two or more 15 ΡΕ2461767 plus ethylenically unsaturated groups. Mean and high molecular weight typically means average molecular weights greater than 700 Daltons.

As used in this application, the term &quot; crosslinker &quot; refers to a compound having at least two ethylenically unsaturated groups. A &quot; crosslinking agent &quot; refers to a cross-linker having a molecular weight of about 700 Daltons or less.

As used in this application, the term &quot; polymer &quot; means a material formed by the polymerization / cross-linking of one or more monomers or macromers or prepolymers.

As used in this application, the term &quot; molecular weight &quot; of a polymeric material (including monomeric or macromeric materials) refers to a weight-average molecular weight unless specifically indicated otherwise or unless the test conditions indicate otherwise.

As used in this application, the term &quot; amino group &quot; refers to a primary or secondary amino group of the formula -NHR ', where R' is hydrogen or an unsubstituted or substituted C1-C20 linear or branched alkyl group, unless specifically indicated otherwise.

As used in this application, the term &quot; polyamine 16 ΡΕ2461767 functionalized by epichlorohydrin &quot; or &quot; epichlorohydrin-functionalized polyamidoamine &quot; refers to a polymer obtained by the reaction of a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial percentage of the amine groups of the polyamine or polyamidoamine to azetidinium groups.

As used in this application, the term &quot; azetidinyl group &quot; refers to a positively charged group of β.

As used in this application, the term &quot; thermally crosslinkable &quot; in reference to a polymeric material or a functional group means that the polymeric material or the functional group can undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively high temperature (drops about 40øC to about 140 ° C), whereas the polymer material or functional group can not be subjected to the same crosslinking reaction (or coupling reaction) with another material or functional group at room temperature (i.e., from about 22 ° C to about 28 ° C, preferably from about 24 ° C to about 26 ° C, in particular at about 25 ° C) to a detectable extent (i.e., greater than about 5%) over a period of about one hour. 17 ΡΕ2461767

As used in this application, the term &quot; phosphorylcholine &quot; refers to a zwitterionic group of O, -O-P-O- (CH2) n-N-R2 O &quot; R 3 in which n is an integral of 1 to 5 and R 1, R 2 and R 3 independently of one another are C 1 -C 8 alkyl or hydroxy C 1 -C 6 alkyl.

As used in this application, the term &quot; reactive vinyl monomer &quot; refers to a vinyl monomer having a carboxyl group or an amino group (i.e., a primary or secondary amino group).

As used in this application, the term &quot; non-reactive hydrophilic vinyl monomer &quot; refers to a hydrophilic vinylic monomer which is free of any carboxyl group or amino group (i.e., primary or secondary amino group). A vinyl non-reactive monomer may include a tertiary or quaternary amino group.

As used in this application, the term &quot; water soluble &quot; in reference to a polymer means that the polymer may be dissolved in water to an extent sufficient to form an aqueous solution of the polymer having a concentration of up to about 30% by weight at ambient temperature (hereinbefore defined). 18 ΡΕ2461767

As used in this application, the term &quot; water contact angle &quot; refers to a contact angle with mean water (i.e., contact angles measured by &quot; Sessile Drop method &quot; which is obtained by calculating the mean of contact angle measurements.

As used in this application, the term &quot; intact &quot; in reference to a coating on a SiHy contact lens is intended to describe the extent to which the contact lens can be stained by Sudan Black in a Stain test by Sudan Black described in Example 1. The good ability of coating a lens of SiHy contact keeping intact means that there is virtually no stain of Sudan Black on the contact lens.

As used in this application, the term &quot; durability &quot; in reference to a coating on a SiHy contact lens is intended to describe that the coating on the SiHy contact lens can survive a digital friction test.

As used in this application, the term &quot; survive a digital friction test &quot; or &quot; surviving a durability test &quot; in reference to a coating on a contact lens means that after digitally rubbing the lens according to a method described in Example 1, the contact angle with water in the digitally rubbed lens is still about 100 degrees or less, preferably about 90 degrees or less, plus 19 ΡΕ2461767 preferably about 80 degrees or less, most preferably about 70 degrees or less. The intrinsic &quot; oxygen permeability &quot;, Dk, of a material is the rate at which oxygen will pass through a material. As used in this application, the term &quot; oxygen permeability (Dk) &quot; in reference to a hydrogel (silicone or non-silicone) or a contact lens means an oxygen permeability (Dk) which is corrected for the surface resistance to the flow of oxygen caused by the boundary layer effect according to the processes set forth in the Examples that follow. Oxygen permeability is conventionally expressed in units of barrers, where &quot; sweeping &quot; is defined as [(cm 3 oxygen) (mm) / (cm 2) (sec) (mm Hg)] xlCT 10. The &quot; oxygen non-transferability &quot;, Dk / t of a lens or material is the rate at which the oxygen will pass through a specific lens or material having a mean thickness of t [in units of mm] over the area to be measure. Transmissibility to oxygen is conventionally expressed in units of barrers / mm, where &quot; barrers / mm &quot; is defined as [(cm 3 oxygen) / (cm 2) (sec) (mm Hg)] x 10-9. &Quot; Ion permeability &quot; through a lens is related to the Coefficient of Ionoflux diffusion. The Ionoflux Diffusion Coefficient, D (in units of [mm2 / min]), is determined by the application of Fick's law 20 ΡΕ2461767 as follows: D - - ΐΐ / (A x dc / dx)

Where n '= ion transport rate [mol / min]; A = area of the exposed lens [mm2]; dc = concentration difference [mol / L]; dx = the thickness of the lens [mm].

As used in this application, the term &quot; ophthalmically compatible &quot; refers to a material or surface of a material that may be in intimate contact with the ocular environment over an extended period without significantly damaging the ocular environment and without significant discomfort to the wearer.

As used in this application, the term &quot; ophthalmically safe &quot; relative to a packaging solution for sterilizing and storing contact lenses is intended to mean that a contact lens stored in the solution is safe to be placed directly on the eye without being washed after autoclaving and that the solution is safe and comfortable enough for daily contact with the eye through the contact lens. An ophthalmically safe packaging solution after autoclaving has a tonicity and pH that are compatible with the eye and is substantially free of ocularly irritating or ocularly cytotoxic materials in accordance with the international ISO standards and FDA rules of the United States. 21 ΡΕ2461767

As used in this application, the term &quot; cut &quot; of a contact lens SiHy refers to a lens section obtained by cutting the lens with a knife or cutting tool at an angle substantially normal to one or other of the anterior and posterior surfaces of the lens. One skilled in the art knows how to cut a contact lens manually (i.e., cut by hand) or with a Cryosta Microtome or a ruler, to obtain a cut of the contact lens. A resulting cut of a contact lens may be polished using ion etching or similar techniques.

The terms &quot; surface modulus &quot;, &quot; surface smoothness &quot;, &quot; elastic modulus of the surface &quot; &quot; Young's modulus of the surface &quot; or surface compression modulus are used interchangeably in this application to mean a nanomechanical property (elastic property) that is measured by atomic force microscopy (AFM) on a surface of a material or a cut of a contact lens in a state of complete (in a phosphate buffered solution, pH 7.3 ± 0.2) using contact mode, nano etching method, Peakforce QNM method, or Harmonic Strength method, as known to one skilled in the art . Jan Domke and Manfred Radmacher reported that the elastic properties of thin films can be measured by AFM (Langmuir 1998, 14, 3320-3325, incorporated herein by reference in its entirety). The nano notch by AFM can be performed according to the experimental protocol described by 22 ΡΕ2461767

González-Méijome JM, Almeida JB and Parafita MA in Microscopy: Science, Technology, Applications and Education, "Analysis of Surface Mechanical Properties of Unworn and Worn Silicone Hydrogel Contact Lenses Using Nanoindentation with AFM", pp. 554-559, A. Méndez -Vilas and J. Díaz (Eds.), Formatex Research Center, Badajoz, Spain (2010), incorporated herein by reference in its entirety. It should be noted that the surface of a cut of a contact lens, not the anterior or posterior surface of a contact lens (as done by González-Méijorne JM, Almeida JB and Parafita MA in its article), is analyzed using nano notch with AFM. The nano notch method, the Peakforce QNM method and the Harmonic Strength method are described in the paper by Kim Sweers, et al. in Nanoscale Research Letters 2011, 6: 270, entitled &quot; Nanomechanical properties of a-synuclin amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM &quot; (incorporated herein by reference in its entirety). It is also understood that when measurements of the elastic modulus of the surface are effected with AFM through a cut of a fully hydrated SiHy contact lens from the anterior surface to the mass or mass to the posterior surface (or vice versa), a surface modulus profile through a cut of a contact lens may be established along a shorter line between the anterior and posterior surfaces on the cut surface of the contact lens. It is further understood that as a good approximation, any experimental amount and directly measured to represent the surface modulus may be used provided that the measured amount is proportional to the surface modulus.

As used in this application, the term &quot; anterior hydrogel layer &quot; in reference to a SiHy contact lens of the invention means a hydrogel layer which includes the anterior surface of the contact lens, which has a substantially uniform thickness (i.e., the variation in thickness is no more than about 10% of the thickness average of that layer) and has an average thickness of at least about 0.1 Âμm. &Quot; average thickness &quot; of an anterior outer hydrogel layer is simply referred to as the &quot; thickness of an anterior external hydrogel layer &quot; this request.

As used in this application, the term &quot; rear outer hydrogel layer &quot; in reference to a SiHy contact lens of the invention means a hydrogel layer which includes the back surface of the contact lens, which has a substantially uniform thickness (i.e., the variation in thickness is no more than about 10% of the thickness average of that layer) and has an average thickness of at least about 0.1 Âμm. &Quot; average thickness &quot; of a posterior exterior hydrogel layer is simply referred to as the &quot; thickness of a posterior hydrogel layer &quot; this request.

As used in this application, the term &quot; inner layer 24 &quot; in reference to a SiHy contact lens of the invention means a layer including a central curved plane (dividing the contact lens into two parts, one containing the front surface and the other containing the back surface) and having a variable thickness.

As used in this application, the term &quot; crosslinked coating &quot; or &quot; hydrogel coating &quot; is used interchangeably to describe a polymeric material cross-linked with a three-dimensional network which may contain water when fully hydrated. The three-dimensional network of a crosslinked polymeric material may be formed by crosslinking two or more linear or branched polymers through crosslinks.

As used in this application, the term &quot; volume increase ratio per water &quot; in reference to an outer, anterior or posterior hydrogel layer of a hydrogel material of a SiHy contact lens of the invention, means a value determined with AFM according to WSR-1 wherein x WSR is the ratio of the volume increase by water of an anterior and posterior hydrogel layer, Lwet is the average thickness of that hydrogel outer layer of the SiHy contact lens in a fully hydrated state as measured by AFM in a cut of the SiHy contact lens in the state fully hydrated (i.e., in a phosphate buffered solution, pH-7.3 + 0.2) and LDry is the average thickness of that outer hydrogel layer 25 ΡΕ 2461767 of the dry contact SiHy contact lens as measured by AFM in a cut of the SiHy contact lens in the dry state (dry without preserving the porosity of the hydrogel material, for example, vacuum drying) and in a substantially dry atmosphere. It is believed that a water-swell ratio of each outer hydrogel layer (of a SiHy contact lens of the invention) is proportional to the water content that each outer hydrogel layer possesses and a ratio of volume increase per water of at least about 100% or 120% WCSHH (whichever is greater, WCSiHy is the water content of the mass (or inner layer of) silicone hydrogel matter of a SiHy contact lens of the invention) may be served as a a good indicator of the nature of the hydrogel outer layers having a higher water content relative to the mass (or inner layer) of the silicone hydrogel material of a SiHy contact lens of the invention.

As used in this application, the term &quot; reduced surface modulus &quot;, in reference to either or both of the outer, anterior and posterior, hydrogel layers of a SiHy contact lens of the invention, is intended to mean a value calculated based on the following equation:

R8M

In which RSM is the reduced modulus of the outer layer, anterior 26 ΡΕ2461767 or later, in hydrogel relative to the inner layer, SMOuter is the surface modulus of the outer layer, posterior or anterior, in hydrogel, and SMInner is the mean surface modulus of the inner layer. SMOuter and SMInner are obtained from a cut surface module profile of the SiHy contact lens in a fully hydrated state (as measured by the analysis of the mechanical properties of the surface, i.e., surface modules of a cut of the contact lens SiHy completely hydrated using AFM), as described above. The profile of the surface module in section (i.e., a graph of the surface modulus versus the distance from one of the front and back surfaces to the other surface along the shorter line between the front and back surfaces on surface of a cut of a lens in SiHy in a fully hydrated state) has at least two outer zones (one including the anterior surface and the other including the posterior surface) and an inner zone (corresponding to the mass material in silicone hydrogel. (ie hydrogel outer layer) is obtained by averaging all surface modules in the outer zone excluding a region of about 1 to about 2 microns between the outer zone and the inner zone ( i.e. within and / or near the boundary region or transition zone).

A &quot; critical friction coefficient &quot; is the tangent of the critical angle which is the steepest angle of an inclined plate in which a lens begins to slide over the inclined plate after being pushed, but stops before, or takes more than 10 seconds to reach the end. Methods for determining the critical coefficient of friction (CDFC) are described in Example 29. The critical friction coefficient (CDFC) of a contact lens is believed to be related to the lubrication of the contact lens surface and may be used to quantify the lubrication of the surface of a contact lens.

As used in this application, &quot; positively charged particulate adherence test &quot; refers to a test to characterize the surface concentration of negatively charged groups (e.g., carboxylic acid groups) of a hydrated SiHi contact lens. The adhesion test of positively charged particles is carried out as follows. An aqueous dispersion of DOWEXâ "¢ 1x4 mesh 20-50 resins, which are spherical, Type I strong base resins (styrene / divinyl benzene copolymers containing N + (CH 3) 3 Cl) and 4% divinyl benzene functional groups) is prepared by dispersing a determined amount of DOWEX ™ 20x4 mesh DOWEX ™ resins in a phosphate buffered saline solution (pH-7.3) to have a resin concentration of 5% by weight and then well blended, shaking or shaking at approximately 1000 rpm for 10 seconds. Silicone hydrogel hydrated contact lenses are immersed in the aqueous dispersion of DOWEXâ "¢ 1x4 mesh 20-50 back resins prepared and swirled at about 1000-1100 rpm for about 1 minute, followed by washing with 28Âμl 2461767 water D1 and vortex in water D1 for about 1 minute. The lenses are then placed in water in glass petri dishes and images of the lenses are taken with a Nikon optical microscope, using backlight. The number of positively charged particles adhered to the surface of each lens can be counted. The number of positively charged particles adhered on the lens surface is proportional to the surface concentration of negatively charged groups of a contact lens.

As used in this application, the term &quot; carboxylic acid &quot;, with reference to the crosslinked coating or hydrogel outer layer of a SiHy contact lens of the invention, means the weight percent of carboxylic group (COOH) based the weight of the crosslinked coating or the hydrogel outer layer of the SiHy contact lens. The carboxylic acid content of a crosslinked coating or a hydrogel outer layer can be theoretically calculated based on the starting material composition to make the crosslinked coating or the hydrogel outer layer and the carboxylic acid content of each starting material . The invention relates to a SiHy contact lens having a layered structural configuration and a single inward water gradient of the SiHy contact lens: a silicon hydrogel core (or mass material) having a below water is completely covered with an outer hydrogel layer (surface) having a water content greater than and having a suitable thickness (at least about 0.1 Âμm) and being substantially free of silicone (preferably totally free of silicone); and the water content of the hydrogel outer layer being at least about 1.2 times (or 120%), preferably at least about 1.3 times (or 130%), more preferably at least about 1.4 times (or 140%), still more preferably at least about 1.5 times (150%), most preferably at least about 2 times (or 200%) of the water content of the mass matter. Figure 1 schematically illustrates a SiHy contact lens having a layered structural configuration, in accordance with a preferred embodiment. According to this preferred embodiment of the invention, the SiHi 100 contact lens has a front surface (or front curve, or convex surface) 101 and an opposing back surface (or base curve or concave surface) 102 that rests on the cornea of the eye when it is worn by a wearer. The contact lens SiHy 100 comprises an inner (or middle) layer 110 and two outer layers 120. The inner layer 110 is the mass matter of the contact lens SiHy 100 and has a three-dimensional shape very close to the contact lens SiHy 100. The inner layer 110 is preferably fabricated into a silicone hydrogel having a lower water content. The two outer layers 120, substantially identical to each other, have a substantially uniform thickness and are fabricated from a substantially silicone-free (preferably totally silicone-free) hydrogel material having a water content of 30 ΡΕ2461767 greater than that of the inner layer 110. The two outer layers 120 merge into the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.

A SiHy contact lens with a layered structural configuration of the invention may offer several advantages over prior art contact lenses. Firstly, such SiHy contact lenses may still have a high oxygen permeability, which is necessary to maintain the health of the cornea of the eye. Secondly, since the inner layer (mass material) gives the mass the mechanical strength and stiffness required for a contact lens, the hydrogel outer layers may have no limits on the water content and may contain as much water as possible. As such, the hydrogel outer layers may provide the contact lens with a skin super enriched with water or with a water content gradient in the structural configuration of the lens (higher water content in the proximal region and including the surface of the lens and water content in the lens core). Thirdly, a SiHy contact lens with a layered structural configuration of the invention may have reduced eye dehydration, may cause less dryness in the eye and, consequently, may provide greater wearing comfort at the end of the day. It is believed that the inner layer (i.e., the lens mass) with a reduced water content will control (limit) the velocity of water diffusion through a lens from 31 ΡΕ2461767 from the back surface to the anterior surface and , in turn, evaporation (loss of water) on the anterior surface of the lens. It is also believed that a layered structural configuration of the invention may create a gradient of inward water concentration (i.e., the water content decreases as it goes inwardly from the anterior surface towards the lens core) which is unfavorable for the diffusion of water through a lens to the posterior surface to the anterior surface based on the Fick diffusion laws. Fourth, a SiHy contact lens with a layered structural configuration of the invention can produce high biocompatibility because the water is highly biocompatible with the tear and because a high water content (e.g., &gt; 75% H2O ) in the hydrogel outer layers is located in and approximates the anterior and posterior surfaces with which the eye is in direct contact and where the biocompatibility counts most. Fifth, the high water content in the hydrogel outer layers of suitable thickness can produce a SiHy contact lens with a very smooth surface, i.e. a &quot; water cushion &quot;. Sixth, a SiHy contact lens in a layered structural configuration of the invention may have a highly lubricated surface. It is believed that the hydrogel outer layer having a much higher water content and having a suitable thickness would produce a &quot; water-loving &quot; which can attract tears to be spread on the surface of the lens. It is believed that the outer layer in a much softer hydrogel than the mass of the lens (the inner layer) may be very susceptible to deformation under pressure (i.e., eyelid cutting forces) and may produce lubrication elastohydrodynamics when this SiHy contact lens is used in the eye. Seventh, a layered structural configuration in a SiHy contact lens of the invention may prevent the silicone from being exposed. The three-dimensional mesh network (i.e., the polymer matrix) of the hydrogel outer layers of suitable thickness is believed to coat the silicone and prevent the silicone from migrating to the lens surface. Eighth, a SiHy contact lens of the invention may have a reduced surface concentration of negatively charged groups (for example, carboxylic acid groups) and is less susceptible to high adherence of debris during handling by the patient and high adherence of proteins during use (it is believed that most proteins in tears are positively charged).

In one aspect, the invention produces a silicone hydrogel hydrated contact lens comprising: an anterior surface (convex) and an opposing posterior (concave) surface; and a layered structural configuration from the front surface to the back surface, wherein the layered structural configuration includes a front hydrogel outer layer, an inner layer on a silicone hydrogel material and a hydrogel rear outer layer, wherein the hydrogel material 33 ΡΕ2461767 has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, still more preferably at least about 90, most preferably at least about 110 barrers, and one

I

The first water content (designated as WCsiHy) is from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, even more preferably from about 15% to about 55%, most preferably from about 15% to about 50% by weight, wherein the outer, back and rear, hydrogel layers have a substantially uniform thickness and merge into the peripheral edge of the lens to completely enclose the inner layer of the silicone hydrogel material, and wherein the hydrogel outer and back layers independently of each other have a second water content greater than WCSiHi as characterized either by having a ratio of volume increase by water of at least about 100% (preferably at least about 150%, more preferably at least about 200%, still more preferably at least about 250%, most preferably p at least about 300%) is WCSiHy &lt; 45%, or having a water-swell ratio of at least about preferably

SiKv

More preferably still more preferably SSH and 34 ΡΕ2461767 are l-WCs,

If WCsiH &gt; 45%, where the thickness of each outer layer in hydrogel is about 0.1 æm to about 20 æm, it preferably drops by about 0.25 æm to about 15 æm, more preferably from about 0 , 5 æm to about 12.5 æm, even more preferably from about 1 æm to about 10 æm (as measured by atomic force microscopy through a posterior surface cut to the anterior surface of the hydrogel contact lens of silicone in a fully hydrated state). Preferably, the anterior and posterior surfaces have a reduced concentration on the surface of negatively charged groups (for example, carboxylic acid groups as characterized by attracting as much as about 200, preferably at most about 160, more preferably at most about 120 , even more preferably at most about 90, most preferably at most about 60 positively charged particles in a positively charged particulate adherence test. Also preferably, the silicone hydrogel hydrated contact lens has a lubricated surface characterized by having a critical coefficient of friction (designated CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less.

According to the invention, the inner layer of a contact lens SiHy is practically the mass matter of the lens. It may be derived directly from a preformed SiHy contact lens 35 in a surface modification process where two outer layers of hydrogel are applied and attached directly and / or indirectly onto the preformed SiHy contact lenses. A preformed SiHy contact lens may be any commercial SiHy lens, such as one of the above described ones. Alternatively, a preformed SiHy may be manufactured according to any methods well known to a person skilled in the art. For example, preformed contact lenses can be produced in a conventional &quot; rotational casting &quot; mold &quot; such as is described, for example, in U.S. Patent No. 3,408,429, or by the total casting process in a static form, as described in U.S. Patents 4,497,198; 5,508,317; 5,583,463; 5,789,464; 5 849 810, or by cutting around silicone hydrogel knobs as used in the manufacture of custom-made contact lenses. In cast molding, a lens formulation is typically molded and cured (i.e., polymerized and / or crosslinked) in molds for making contact lenses. For the production of preformed SiHy contact lenses, a SiHy lens formulation for cast casting or spin casting or for manufacturing SiHy rods used in the shear-cutting of contact lenses generally comprises at least a component selected from the group consisting of a silicone-containing vinyl monomer, a silicone-containing vinyl macromer, a silicone-containing prepolymer, a hydrophilic vinylic monomer, a hydrophobic vinylic monomer, a crosslinking agent (a compound having a molecular weight of about of 700 Daltons or less and containing at least two ethylenically unsaturated groups), a free radical initiator (photoinitiator or thermal initiator), a hydrophilic vinyl macromer / prepolymer, and combinations thereof, well known to a person skilled in the art. A formulation for SiHy contact lenses may also comprise other necessary components known to a person skilled in the art, such as, for example, a UV-absorbing agent, a coloring agent with visibility (for example, dyes, pigments or mixtures thereof ), antimicrobial agents (for example, preferably silver nanoparticles), a bioactive agent, leaching lubricants, leach tear stabilizers and mixtures thereof, as are known to a person skilled in the art. The resulting preformed SiHy contact lenses may then be subjected to extraction with an extraction solvent to remove unpolymerized components from the resulting lenses and to a hydration process well known to a person skilled in the art. In addition, a preformed SiHy contact lens may be a colored contact lens (i.e., a SiHy contact lens with at least one colored pattern printed thereon, as is well known to a person skilled in the art) .

Any silicone-containing vinyl monomers that are suitable may be used in the invention. Examples 37 and 2461767 of preferred silicone-containing vinyl monomers include, without limitation, N- [tris (trimethylsiloxy) silylpropyl] (meth) acrylamide, N- [tris (dimethylpropylsiloxy) silylpropyl] (meth) acrylamide, N- [(tris (dimethylethylsiloxy) silylpropyl] - (meth) acrylamide, N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propylacrylamide, N- (bis (trimethylsilyloxy) methylsilyl) propyl] -2-methylacrylamide; (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) -2-methylacrylamide; propyl] -acrylamide N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] -2-methylacrylamide N, N-bis [2-hydroxy- 3- (3- (tris- (trimethylsilyloxy) silyl) propyl oxy) -propyl] acrylamide; N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) -propyloxy) -propyl] -2-methacrylamide; N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) pro-pyloxy) propyl] acrylamide; N, N-bis [2-hydroxy-3- (3-t-butyldimethylsilyloxy) propyloxy) propyl] -2-methylacrylamide N, N-bis [2-hydroxy- 3-methacryloxypropylpenta-methyldisiloxane methacrylate, tris (trimethylsilyloxy) silylpropyl methacrylate (TRIS), (3-methyryloxy-2-hydroxypropyloxy) pro-pivalbis (trimethylsiloxy) methylsilane) , 3-methacryloxy-2-hydroxyethoxy) propylbis (trimethylsiloxy) methylsilane, N-2-methacryloxy carbamate, 3-methacryloxy- (trimethylsiloxy-3-propyl) silyl carbamate, 3- (trimethylsilyl) propylvinyl, 3- (vinyloxycarbonylthio) propyl-tris- (trimethylsiloxy) silane carbonate, 3- [ tris (trimetylsiloxy) silyl] propylvinyl carbamate, 3- [tris (trimethylsiloxy) silyl] propylalyl carbamate, 3- [tris (trimethylsiloxy) silyl] propylvinyl carbonate, t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate; and trimethylsilylmethyl vinyl carbonate). More preferred siloxane containing (meth) acrylamide monomers of formula (1) are N- [tris (trimethylsiloxy) silylpropyl] acrylamide, TRIS, N- (2-hydroxy-3- (3- (t-butyldimethylsilyl) propyl yloxy) propyl] acrylamide, or combinations thereof.

A preferred class of silicone-containing vinyl monomers or macromers are polysiloxane-containing vinyl monomers or macromers. Examples of such polysiloxane-containing vinyl monomers or macromers are monomethacrylated or monoacrylated polydimethylsiloxanes of various molecular weights (e.g., mono-3-methacryloxypropyl terminated, mono-butyl terminated polydimethylsiloxane or mono- (3-methacryloxy-2-hydroxy-propyloxy terminated ) propyl, mono-butyl terminated polydimethylsiloxane); polydimethylsiloxanes of various dimethacrylated or diacrylated molecular weights; vinyl carbonate terminated polydimethylsiloxanes; vinyl carbamate terminated polydimethylsiloxane; polydimethylsiloxanes of various vinyl-terminated molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; polydimethylsiloxanes 39 ΡΕ2461767 terminated by acrylate; methacrylate-terminated polydimethylsiloxanes; vinyl carbonate terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxy-propyl polydimethylsiloxane; N, N, N ', N'-tetrakis (3-methacryloxy-2-hydroxypropyloxy) -alpha, omega-bis-3-amino-propyl-poly-dimethylsiloxane; polysiloxanylalkyl (meth) acrylic monomers; macromer selected from the group consisting of Macromer A, Macromer B, Macromer C and Macromer D described in US 5,760,100 (incorporated herein by reference in its entirety); the reaction products of glycidyl methacrylate with amino-functional polydimethylsiloxanes; hydroxyl functionalized siloxane-containing vinyl monomers or macromers; polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4 136 250, 4 153 641, 4 182 822, 4 189 546, 4 343 927, 4 254 248, 4 355 147, 4 276 402, 4 327 203, 4 341 889 , 4,486,547, 4,543,398, 4,560,512, 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, 4,954,587, 5,010,145, 5,034,461, 070 170, 5 079 319, 5 039 761, 5 346 946, 5 358 995, 5 387 632, 5 416 132, 5 451 617, 5 486 579, 5 962 548, 5 981 675, 5 039 913 and 6 762 264 (incorporated herein by reference in their entirety); macromers containing polysiloxane disclosed in U.S. Patents 4,259,467, 4,260,725 and 4,261,875 (incorporated herein by reference in their entirety). Di-and triblock macromers consisting of polydimethylsiloxane and polyalkylene oxides may also have utility. For example, polyethyleneoxide-block-polydimethylsiloxane-block-polyethylene oxide-capped at the end may be used with methacrylate to enhance oxygen permeability. Suitable vinyl monomers / macromers containing monofunctional hydroxyl-functionalized siloxane and suitable vinyl monomers / macromers containing multifunctional hydroxyl-functionalized siloxane are available from Gelest, Inc, Morrisville, PA.

Another class of preferred silicone-containing macromers are the silicone-containing prepolymers comprising hydrophilic segments and hydrophobic segments. Any suitable prepolymer containing silicone, with hydrophilic segments and hydrophobic segments can be used in the invention. Examples of such silicone-containing prepolymers include those described in co-proprietary patents Nos. 6 039 913, 7 091 283, 7 268 189 and 7 238 750, 7 521 519; in co-owned U.S. patent applications U.S. 2008-0015315A1, U.S. 2008-0143958A1, U.S. 2,008-0143-033A1, U.S. 2008-0234457A1, U.S.A. 2008-0231798A1, and U.S. co-owners No 61/180 449 and 61/180 453; all of which are hereby incorporated by reference in their entirety.

Examples of preferred hydrophilic vinyl monomers are N, N-dimethylacrylamide (DMA), N, N-dimethyl-methacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acrylaminoyl-1-propanol, N-hydroxyethylacrylamide, N- 3-methylene-2-pyrrolidone, 1-methyl-5-methylene-4α, 4-methylene-2-pyrrolidone, 2-ethylene- pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-isopropyl-3-methylene- 3-methylene-2-pyrrolidone, 2-hydroxyethylmethacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydro propylmethacrylate hydrochloride, aminopropyl methacrylate, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidon (meth) acrylate having a molecular weight of up to 1500, on average weighted, methacrylic acid, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinylformamide, N-vinyl-N-methylacetamide, allyl alcohol, N-vinyl caprolactam and mixtures thereof.

Examples of preferred vinylic hydrophobic monomers include methyl acrylate, ethyl acrylate, propyl acrylate, isopropylacrylate, cyclohexylacrylate, 2-ethylhexylacrylate, methylmethacrylate, ethylmethacrylate, propylmethacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene , vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyl toluene, vinylethyl ether, perfluorohexylethyl-thiocarbonylaminoethyl methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, isopropyl methacrylate, hexafluorobutyl methacrylate.

Examples of preferred crosslinking agents include, without limitation, tetraethyleneglycol diacrylate, triethyleneglycol diacrylate, ethylene glycol diacrylate, diethyleneglycol diacrylate, tetraethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, trimethyl propane trimethacrylate , pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylene diamine dimethyl acrylamide, ethylenediamine diacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallyl cyanurate, allyl methacrylate, 1,3-bis (methacrylamidopropyl) N, N'-methylene bisacrylamide, N, N'-methylenebis (meth) acrylamide, N, N'-ethylene bisacrylamide, N, N'-ethylenebis (methacrylamide) , 1,3-bis (N-methacrylamidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacrylamidobutyl) -1,1,3,3-tetrakis (trimethylsiloxy) - disiloxane, 1,3-bis (acrylamidopropyl) yl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacryloxyethylureidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) -dissiloxane and combinations thereof. A preferred crosslinking agent is tetra (ethylene glycol) diacrylate, tri (ethylene glycol) diacrylate, ethylene glycol, di (ethylene glycol) diacrylate, methylene bisacrylamide diacrylate, triallyl isocyanurate or triallyl cyanurate. The amount of the crosslinking agent used is expressed in the weight content relative to the total polymer and preferably in the range of about 0.05% to about 4%, and more preferably in the range of about 0.01% 1% to about 2%.

Examples of suitable thermal initiators include, but are not limited to, 2,2'-azobis (2,4-dimethylpentanenitrile), 2,2'-azobis (2-methylpropanenitrile), 2,2'-azobis (2-methylbutanenitrile) , peroxides such as benzoyl peroxide and the like. Preferably, the thermal initiator is 2,2'-azobis (isobutyronitrile) (AIBN).

Suitable photoinitiators are benzoin methylether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexylphenylketone and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide; bis- (2,6-dichlorobenzoyl) -4-N-propylphenylphosphine oxide; and bis- (2,6-dichlorobenzoyl) -4-N-butylphenylphosphine oxide. Reactive photoinitiators which may be incorporated, for example, into a macromer or can be used as a special monomer are also suitable. Examples of photoinitiators are those disclosed in EP 632 329, incorporated herein by reference in their entirety. The polymerization can then be driven by actinic radiation, for example light, in particular UV light of a suitable wavelength. Spectral requirements can be controlled accordingly by the addition of suitable photosensitizers. 44 ΡΕ2461767

Any polymerizable agents suitable for UV absorption may be used in the invention. Preferably, a UV absorbing agent comprises a benzotriazole moiety or a benzophenone moiety. Examples of polymerizable UV absorbers include, without limitation, 2- (2-hydroxy-5-vinylphenyl) -2H-benzotriazole, 2- (2-hydroxy-5-acryloyloxyphenyl) -2H-benzotriazole, 2- (2- (2'-hydroxy-5'-methacrylamidophenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-5'-methacrylamidophenyl) -5-methoxybenzotriazole, 2- (2'-Hydroxy-5'-methacryloxypropyl-3'-t-butyl-phenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-5'-methacryloxyethylphenyl) -benzotriazole, 2- (2'-hydroxy -5'-methacryloxypropylphenyl) benzotriazole, 2-hydroxy-4-methacryloxybenzophenone. The bioactive agent is any compound that can prevent a disease in the eye or reduce the symptoms of a disease in the eye. The bioactive agent may be a medicament, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid or any combination thereof. Examples of medicaments useful herein include, but are not limited to, rebamipid, ketotifen, olaptidine, chromoglycolate, cyclosporin, nedocromil, levocabastine, lodoxamide, ketotifen or the pharmaceutically acceptable salt or ester thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha-hydroxy acids (e.g., glycolic, lactic, malic, tartaric, mandelic and citric acids and salts thereof, etc.), linoleic acids and ΡΕ2461767 gamma, and vitamins (e.g., B5, A, 6, etc.).

Examples of leachable lubricants include, without limitation, mucin-like materials (e.g., polyglycolic acid) and non-crosslinkable hydrophilic polymers (i.e., without ethylenically unsaturated groups). Any hydrophilic polymers or copolymers without any ethylenically unsaturated groups may be used as leachable lubricants. Preferred examples of non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, a homopolymer of a vinyl lactam, a copolymer of at least one vinyl lactam in the presence or absence of one or more vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, vinyl acetate copolymers, polypropylene copolymers, polypropylene copolymers, polypropylene copolymers, polypropylene glycol copolymers, polyacrylic acid, poly-2-ethyloxazoline, heparin polysaccharides, polysaccharides and mixtures thereof. The weight-average molecular weight Mw of the non-crosslinkable hydrophilic polymer is preferably from 5,000 to 1,000,000.

Examples of leachable tear stabilizing agents include, without limitation, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingol glycolipids, fatty alcohols, fatty acids, mineral oils and mixtures thereof. Preferably, a tear stabilizing agent is a phospholipid, a monoglyceride, a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, a sphingolipid, a sphingol glycolipid, a fatty acid having 8 to 36 carbon atoms, a fatty alcohol having 8 to 36 carbon atoms or a mixture thereof.

According to the invention, a formulation for SiHy lens may be a solution or a melt of a temperature of from about 20øC to about 85øC. Preferably, a polymerizable composition is a solution of all desirable components in a suitable solvent or in a mixture of suitable solvents.

A formulation for SiHy lens may be prepared by dissolving all desirable components in any suitable solvent, such as water, a mixture of water and one or more water miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents as are known to a person skilled in the art.

An example of preferred organic solvents includes, without limitation, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.), n-butyl ether of diethyleneglycol ether, diethyleneglycol methyl ether, ethylene glycol ether, propylene glycol methyl ether, propylene glycol acetate methyl ether, dipropylene glycol acetate methyl ether, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, n- propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methyl 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorbomeol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2- heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norbomeol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl -3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol , 2-methyl-2-octanol, 2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol , 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-3-octanol, 3-methyl-3-octanol, 3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-eptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1 3-methyl-1-butene, 4-hydroxy-4-methylcyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol 2,3, 4-trimethyl-3-pentanol, 3,7-dimethyl-3- ΡΕ2461767 octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl- amyl, isopropanol, 1-methyl-2-pyrrolidone, N, N-dimethylpropionamide, dimethylformamide, dimethylacetamide, dimethylpropionamide, N-methylpyrrolidinone and mixtures thereof.

Numerous formulations for lenses in SiHy have been described in numerous patents and patent applications published at the time of submission of this application. All of these can be used to obtain a preformed lens in SiHy which in turn becomes the inner layer of a SiHy contact lens of the invention, provided that they produce a SiHy material having a Dk and water content as above we have specified. A lens formulation in SiHy to make commercial SiHy lenses, such as lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, filcon II 3, also may be used in the manufacture of preformed SiHy contact lenses (the inner layer of a SiHy contact lens of the invention).

Lens molds for making contact lenses are well known to the person skilled in the art and, for example, are used in casting or cast casting. For example, a mold (for casting) generally comprises at least two mold sections (or portions) or mold halves, i.e. first and second mold halves. The first half of the mold 49 defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second halves are configured to receive the other so that the lens forming cavity is formed between the first molding surface and the second molding surface. The molding surface of a mold half is the surface of the mold forming the cavity and is in direct contact with the lens forming material.

Methods for fabricating mold sections for casting a contact lens are generally well known to those of ordinary skill in the art. The process of the present invention is not limited to any particular method of forming a mold. Indeed, any method of forming a mold can be used in the present invention. The first and second mold halves may be formed by various techniques, such as injection molding or lathe work. Examples of suitable processes for forming the mold halves are disclosed in U.S. Patents 4,474,711 to Schad; 4,460,534 to Boehm et al; 5,843,346 to Morrill; and 5,894,002 to Boneberger et al., which are also incorporated herein by reference.

Virtually all materials known in the art of making molds can be used to make molds for the manufacture of contact lenses. For example, polymeric materials, such as polyethylene, 50 ΡΕ2461767 polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (transparent amorphous ethylene norbornene copolymer from Ticona GmbH, Frankfurt, Germany and Summit, New Jersey), or may be used. Other materials that allow the transmission of UV light, such as quartz glass and sapphire, may be used.

In a preferred embodiment, reusable molds are used and the silicone hydrogel lens forming composition is actinically cured under a spatial limitation of actinic radiation to form a SiHi contact lens. Examples of preferred reusable molds are those disclosed in U.S. Patent Applications 08 / 274,942, filed July 14, 1994, 10 / 732,566, filed December 10, 2003, 10 / 721,913, filed November 25, 2003 and Patent No. 6,627,124, which are incorporated by reference in their entirety. The reusable molds may be made of quartz, glass, sapphire, CaF2, a cyclic olefin copolymer (such as, for example, Topas® COC grade 8007-S10 (transparent amorphous ethylene norbornene copolymer) from Ticona GmbH, Frankfurt, Germany and Summit, New Jersey, Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY), polymethylmethacrylate (PMMA), DuPont polyoxymethylene (Delrin), Ultem® (polyetherimide) from GE Plastics, PrimoSpire®, etc.

According to the invention, the silicone hydrogel (mass material) of the inner layer has an oxygen permeability of at least about ΟΊ 0, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 barrers, most preferably at least about 110 Barrers. The silicone hydrogel material may also have a (first) WCSiHy water content of from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%; even more preferably, from about 15% to about 55%, most preferably from about 15% to about 50% by weight. The silicone hydrogel material may further have an elastic modulus of mass or Young's modulus of mass (the terms &quot; softness &quot;, &quot; elastic modulus &quot; &quot; Young's modulus &quot; are used interchangeably hereinbefore to mean elastic modulus if the term is not modified by the word &quot; surface &quot;) from about 0.3 MPa to about 1.8 MPa, preferably from 0.4 MPa to about 1.5 MPa, more preferably from about 0 , 5 MPa to about 1.2 MPa. The oxygen permeability, elastic modulus and water content of the inner layer of the silicone hydrogel material of a SiHy contact lens of the invention can be determined by measuring the oxygen permeability, elastic modulus and water content of the lens in SiHy preformed layer from which the inner layer is derived. It will be understood that, as a reasonable approximation, the elastic modulus of a SiHy contact lens of the invention may be considered to be the elastic modulus of the silicone hydrogel matter of the inner layer 52Ρ242471767 because the outer hydrogel layers are much thinner . One skilled in the art is well aware of how to determine the elastic modulus and the water content of a silicone hydrogel material or a SiHy contact lens. For example, all commercial contact lenses in SiHy reported values of elastic modulus and water content.

The two hydrogel outer layers of a SiHy contact lens of the invention are preferably substantially identical to each other and are a crosslinked coating which is applied over a preformed SiHy contact lens having the desired Dk, water content and modulus elastic mass. The configuration of the layered structure of a SiHy contact lens of the invention may be established by atomic force microscopy (AFM) analysis of a cut of a SiHy contact lens in a fully hydrated state (i.e. directly in water or in a solution buffered saline) as described above and set forth in the Examples. The surface modules of a cut can be characterized (by image) with AFM (for example, Force-Volume mode) to visualize any changes in the surface modulus from the back surface side to the anterior surface side through the cut. A significant change (e.g., about 20% or more, preferably about 30% or more) observed in the surface modulus (examining the AFM image 534246767) about a thickness of about 0.04 μm, preferably about 0.03 Âμm, more preferably about 0.02 Âμm, even more preferably about 0.01 Âμm along the shorter line between the anterior and posterior surfaces through a cut of the SiHy contact lens in the fully hydrated state indicates a transition from one layer to a different layer. The average thickness of each outer layer in hydrogel can be determined from the AFM image as is well known to the person skilled in the art.

The two hydrogel outer layers of a SiHy contact lens of the invention have a substantially uniform thickness. They melt at the peripheral edge of the contact lens to completely enclose the inner layer of the silicone hydrogel material. The thickness of each outer hydrogel layer is from about 0.1 Âμm to about 20 Âμm, preferably from about 0.25 Âμm to about 15 Âμm, still more preferably from about 0.5 Âμm to about 12 Âμm , 5 μm, most preferably from about 1 μm to about 10 μm. The thickness of the hydrogel outer layers (or crosslinked coating) of a SiHy contact lens of the invention is determined by AFM analysis of a cut of the SiHy contact lens in a fully hydrated state as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably at least 54 ΡΕ2461767 maximum about 10% (10% or less) of the thickness of the contact lens SiHy cent in fully hydrated state.

It is to be understood that the configuration of the layered structure of a SiHy contact lens of the invention may also be established qualitatively by electron scanning (SEM) scanning of a cut of the lyophilized SiHy contact lens as set forth in the Examples. SEM can present the different compositions and / or structures of each layer of a cut of the SiHy contact lens in a freeze-dried state. A significant change (e.g., about 20% or more, preferably about 30% or more) observed in the compositions and / or significant changes (noted in view) in the structures (upon examination of the SEM image) over a thickness of about 0.04 μm, preferably about 0.03 μm, more preferably about 0.02 μm, even more preferably about 0.01 μm, through a cut of the SiHy contact lens in a lyophilized state indicates a transition from one layer to a different layer. However, the thickness value based on SEM analysis of a cut of a SiHy lens in the lyophilized state is typically less than the present value because of the collapse of the hydrogel outer layers, the transition layer, if applicable, and the layer lyophilized.

According to this aspect of the invention, the two hydrogel outer layers (the anterior and posterior hydrogel outer layers) of a contact lens 55 ΡΕ2461767

SiHy of the invention comprise a (second) water content which should be higher than the (first) water content (WCs ± Hy) of the inner layer of the silicone hydrogel material and, more specifically, should be at least about 1, 2 times (i.e., 120%) of the (first) water content (WCsiHy) of the inner layer of the silicone hydrogel material. The proportion of water volume increase of each of the hydrogel outer layers is believed to relate to their water content and, as a good approximation, may reasonably represent the water content of the outer hydrogel layer. In alternatively preferred embodiments, where the water content (WCsiHy) of the inner layer of the silicone hydrogel material is about 55% or less, the ratio of the volume increase per water of each outer layer to hydrogel is at least of about 150%; where the water content (WCsiHy) of the inner layer of the silicone hydrogel material is about 60% or less, the ratio of the volume increase per water of each outer layer to hydrogel is at least about 200%; where the water content (WCsiHy) of the inner layer of the silicone hydrogel material is about 65% or less, the ratio of the volume increase per water of each outer layer to hydrogel is at least about 250%; where the water content (WCsiHy) of the inner layer of the silicone hydrogel material is about 70% or less, the ratio of the volume increase per water of each outer layer to hydrogel is at least about 300%

It is understood that the water content of the anterior and posterior outer layers of hydrogel (the crosslinked coating) can be determined more accurately according to the processes described in Example 23. Alternatively, the water content of the two layers (the crosslinked coating) may be determined with an article comprising a thin substrate that does not absorb water according to the coating process identical to the SiHi contact lens under substantially identical conditions. The water content of each outer hydrogel layer can then be determined based on the difference between dry and hydrated weights of the article with the crosslinked coating.

According to the invention, each of the two hydrogel outer layers is substantially free of silicone, preferably totally free of silicone. However, it is well known that when X-ray photoelectron spectroscopy (XPS) is used to establish the presence or absence of silicone in the hydrogel outer layer (generally a depth per probe of 1.5 to 6 nm), samples are inevitably contaminated by environmental silicon as shown by XPS detection of silicon on surfaces of samples which are theoretically free of any silicon atom, such as, for example, a polyethylene sheet, a DAILIES® AquaComfortPlus ™ contact lens from CIBA VISION Corporation or an ACUVUE® Moist from Johnson &amp; Johnson (see Example 21 below). Thus, the term &quot; substantially free of silicon &quot; is used in this application to mean that an atomic percentage of surface silicon measured by XPS in a SiHy contact lens is less than about 200%, preferably less than about 175%, more preferably less than 150%, even more preferably less than 125% of the atomic percentage of silicon of a control sample known to be inherently (theoretically) silicon-free (for example, a polyethylene sheet, a DAILIES® AquaComfortPlus ™ contact lens from CIBA VISION Corporation or an ACUVUE® Moist, Johson & Johnson). Alternatively, each outer hydrogel layer of a SiHy contact lens of the invention is substantially free of silicon, as characterized by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, of the total elemental percentage, as measured by XPS analysis of the contact lens in the dry state. It is to be understood that a small percentage of silicone may optionally (but not preferably) be incorporated into the polymer network of the hydrogel outer layer as long as it does not significantly impair the surface properties (hydrophilicity, wetting and / or lubrication) of a lens SiHy contact.

In a preferred embodiment, the hydrogel front and back layers (the crosslinked coating) have a sufficient crosslinking density (or crosslink density) reduced to produce the crosslinked coating or the outer layers 58 ΡΕ2461767 in hydrogel (i.e. is the contact lens SiHy) with a high resistance to digital friction such as characterized in that it does not have visible surface cracks under a dark field after the contact lens SiHy has been rubbed between the fingers. Surface friction induced by digital friction is believed to reduce surface lubrication and / or may not be able to prevent the silicone from migrating over the surface (exposure). Surface cracking may also indicate excessive crosslinking density in the surface layers that may affect the surface elastic modulus. Preferably, the silicone-free hydrogel material in the hydrogel outer layers (the crosslinked coating) comprises crosslinks derived from azetidinium groups in a thermally induced coupling reaction.

In another preferred embodiment, the front and back surfaces have a reduced surface concentration of negatively charged groups including carboxylic acid groups as characterized by attracting at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, most preferably at most about 60 positively charged particles in a positively charged particulate adherence test. It is desirable to have a minimal surface concentration of negatively charged groups (for example, carboxylic acid groups) on a SiHi contact lens of the invention, because contact lenses 59 ΡΕ2461767 with a high concentration of negatively charged groups (e.g. carboxylic acid) are susceptible to high adherence of debris during handling by the patient, high adherence of proteins during use (a majority of proteins in tears are believed to be positively charged) high deposition and accumulation of antimicrobials such as Poly- hexamethylene biguanide (PHMB) present in contact lens care solutions. To have a reduced surface concentration of negatively charged groups (for example, carboxylic acid groups), the outer, front and back hydrogel layers should have a relatively low carboxylic acid content. Preferably, the hydrogel outer and back layers have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, still more preferably about 10% by weight or less , most preferably about 5% by weight or less.

In another preferred embodiment, a SiHy contact lens of the invention has good surface lubrication characterized by having a critical coefficient of friction (designated as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, a contact lens of the invention preferably has about 0.043 or less, more preferably about 0.040 or less. Alternatively, a contact lens 60 ΡΕ2461767

SiHy of the invention preferably has better lubrication than ACUVUE OASYS or ACUVUE TruEye as measured in a blind test in accordance with the lubrication evaluation procedures described in Example 1.

In another preferred embodiment, a SiHy contact lens of the invention further comprises, in its layered structural configuration, two transition layers of polymer material (s) as is schematically illustrated in Figure 2. Each of the two transition layers 115 is located between the inner layer 110 and one of the two hydrogel outer layers 120. Each transition layer has a substantially uniform thickness. The thickness of each transition layer is at least about 0.05 μm, preferably from about 0.05 μm to about 10 μm, more preferably from about 0.1 μm to about 7.5 μm, still more preferably from about 0.15 Âμm to about 5 Âμm. The transition layers fuse at the peripheral edge of the contact lens to completely enclose the inner layer of the silicone hydrogel material. The presence and thickness of the transition layers may be determined by preferably AFM analysis of a cut of the SiHy contact lens in a fully hydrated state as described above for the outer layers and hydrogel inner layers.

The two transition layers of a SiHy contact lens of the invention are essentially a base (or primer) coating which is applied over a preformed SiHy contact lens having a Dk, water content and elastic modulus of before the crosslinked coating (the outer layers in hydrogel) is applied above. The transition layers (base coat) function to anchor / attack the outer layers in hydrogel. Preferably, the transition layers comprise a carboxyl-containing polymer (COOH), preferably a homo or copolymer of acrylic acid or methacrylic acid or C2-C12 alkylacrylic acid. It is to be understood that the carboxyl-containing polymer can penetrate the mass matter and extend it into the outer layers in hydrogel. When such penetration occurs in the inner layer of the silicone hydrogel material, each transition layer would comprise the carboxyl-containing polymer and the silicone hydrogel which are interconnected together. It is also believed that the presence of the transition layers, especially when comprising a carboxyl-containing polymer, can produce a relatively high water content in a thicker layer and / or a water reservoir for the hydrogel outer layers, due to the properties of the carboxylic groups bind to water. Furthermore, even if the transition layer could contain high carboxylic acid groups, it would have a minimal adverse impact on the surface concentration of carboxylic acid groups of the SiHi contact lens because the surface concentration of carboxylic acid groups is predominantly determined by outer layers in hydrogel that completely cover the transition layer 62 ΡΕ2461767. The hydrogel outer layers with a reduced surface concentration of carboxylic acid groups can prevent the deposition of positively charged proteins from the tears of a patient using the lens.

In another preferred embodiment, the hydrogel anterior and posterior outer layers independent of each other have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30% , still more preferably at least about 35%, most preferably at least about 40%, relative to the inner layer.

The hydrogel front and back outer layers are preferably fabricated in the same or substantially identical (or substantially identical) material (s), and may be formed by the application and cross-linking of a polymeric material water-soluble crosslinkable hydrophilic resin on a preformed SiHy contact lens comprising amino and / or carboxyl groups, wherein the preformed SiHy contact lens becomes the inner layer after cross-linking.

According to the invention, a preformed SiHy contact lens either can inherently comprise, or be modified to comprise, amino groups and / or carboxyl groups on and / or near its surface. 63 ΡΕ2461767

When a preformed SiHy contact lens comprises amino groups and / or carboxyl groups on and / or near its surface, it is obtained by the polymerization of a silicone hydrogel lens comprising a reactive vinyl monomer.

Examples of preferred reactive vinyl monomers include, without limitation, amino-C 2 -C 6 -alkyl (meth) acrylate, C 1 -C 6 -alkylamino (meth) acrylate, allylamine, vinylamine, (meth) acrylamide of amino-C 2 -C 6 alkyl (meth) acrylamide, acrylic acid, C 1 -C 12 -alkyl acrylic acid, methacrylic acid, ethyl acrylic acid, ), N-N-2-acrylamide glycolic acid, beta methyl acrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4 1,3-itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof. Preferably, the contact lens SiHy is fabricated from a lens formulation comprising at least one reactive vinyl monomer selected from the group consisting of amino-C 2 -C 6 -alkyl (meth) acrylate C 1 -C 6 -alkylamino-C 2 -C 6 -alkylamino, allylamine, vinylamine, (C 1 -C 6) -alkylamino (meth) acylamide, C 1 -C 6 -alkylamino-C 2 -C 6 -alkylamido , acrylic acid, C1-C12 alkylacrylic acid, N, γ-2-acrylamidoglycolic acid and combinations thereof. The lens formulation preferably comprises from about 0.1% to about 10%, more preferably from about 0.25% to about 7%, still more preferably from about 0.5% to about 5%, and more preferably from about 0.75% to about 3% by weight of a reactive vinylic monomer described above.

A preformed SiHy contact lens may also be subjected to either a surface treatment to form a reactive base coat having amino groups and / or carboxyl groups on the surface of the contact lens. Examples of surface treatments include, without limitation, surface treatment by energy (e.g. plasma, static electric charge, irradiation or other source of energy), chemical treatments, chemical vapor deposition, grafting of hydrophilic vinyl monomers or macromers on the surface of an article, coating layer by layer (&quot; LbL coating &quot;, LbL = layer by layer) obtained according to methods described in U.S. Patent Serial Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805 and 6,896,926 and in U.S. Patent Applications Publication Nos. 2007 / 0229758A1, 2008 / 0152800A1, and 2008 / 0226922A1, (incorporated by reference herein in their entirety). As used herein, &quot; LbL coating &quot; refers to a coating that is not covalently bonded to the polymer matrix of a contact lens and is obtained by layer-to-layer ("LbL") deposition of charged or chargeable (by protonation or deprotonation) materials and / or not loaded onto the lens. An LbL coating may be composed of one or more layers.

Preferably, the surface treatment is a LbL coating process. In this preferred embodiment (i.e., the reactive LbL base coat embodiment), a resulting silicone hydrogel contact lens comprises a reactive LbL base coat (i.e., the two transition layers) comprising at least a layer of a reactive polymer (i.e., a polymer having pendant amino groups and / or carboxyl groups), wherein the reactive LbL base coat is obtained by contacting the contact lens with a solution of a reactive polymer. Contact of a contact lens with a coating solution of a reactive polymer may occur by immersing it in the coating solution or by vaporizing it with the coating solution. A contacting process involves simply immersing the contact lens in a bath of a coating solution over a period of time or, alternatively, immersing the contact lens sequentially in a series of baths of coating solutions for a shorter, fixed time to each bath. Another contact process involves only the vaporization of a coating solution. However, one of ordinary skill in the art can design a number of alternatives involving various combinations of the steps of vaporizing - and dipping. The contact time of a contact lens with a coating solution of a reactive polymer may last up to about 10 minutes, preferably from about 5 to about 360 seconds, more preferably from about 5 to about 250 seconds, further preferably from about 5 to about 200 seconds.

According to this reactive base coating embodiment LbL, the reactive polymer may be a linear or branched polymer having pendant amino groups and / or carboxyl groups. Any polymers having pendant amino groups and / or carboxyl groups may be used as the reactive polymer to form base coatings on silicone hydrogel contact lenses. Examples of such reactive polymers include, without limitation: a homopolymer of a reactive vinyl monomer; a copolymer of two or more reactive vinyl monomers; a copolymer of a vinyl monomer reactive with one or more non-reactive hydrophilic vinylic monomers (i.e. hydrophilic vinyl monomers free of any carboxyl or amino group (primary or secondary); polyethyleneimine (PEI); polyvinyl alcohol with pendant amino groups; a carboxyl-containing cellulose (for example, carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose), hyaluronate, chondrotin sulfate, poly (glutamic acid), poly (aspartic acid), and combinations thereof 67 ΡΕ2461767

Any preferred reactive vinyl monomers described above may be used in this embodiment to form a reactive polymer intended to form a reactive base coating LbL. incorporated herein by

Preferred examples of carboxyl-free non-reactive hydrophilic vinyl monomers or amino group include, without limitation: acrylamide (AAm), methacrylamide N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone N-dimethylaminoethyl acrylate (DMAEA), N, N-dimethylaminopropylmethacrylamide (DMAPMAm), N, N-dimethylaminopropylacrylamide (DMAPPAAm), glycerol methacrylate, 3-acryloylamino- 1-propanol, N-hydroxyethyl acrylamide, N- [tris (hydroxymethyl) methyl] acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 2-pyrrolidone, 5-methylene-2-pyrrolidone, 5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 2-hydroxyethyl acrylate, hydroxypropyl (meth) acrylate, C1-4 alkoxy (meth) acrylate (meth) acrylate having a weight average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl- N-methyl-acetamide, allyl alcohol, vinyl alcohol (hydrolyzed vinyl acetate form in the copolymer), a vinyl monomer containing phosphorylcholine (including (meth) acryloyloxyethylphosphorylcholine and those described in U.S. Patent No. 5,461,433, in their entirety), and combinations thereof.

Preferably the reactive polymers to form a reactive base coating LbL are polyacrylic acid, polymethacrylic acid, poly (C2 -C12 alkylacrylic acid), poly (acrylic acid-methacrylic acid), poly (C2 -C12 alkyl acrylic acid- (meth) acrylic acid], poly (N, Ν-2-acrylamidoglycolic acid), poly [(meth) acrylic-coacrylamide], poly [(meth) acrylic-co-vinylpyrrolidone], poly C 2 -C 12 -alkyl acrylamide], poly [C 2 -C 12 -alkyl vinyl pyrrolidone] acrylic acid, poly (hydroxylated (meth) acrylic-co-vinyl acetate), poly [C 2 -C 12 -alkyl acrylic acid (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or combinations thereof. The weight-average molecular weight Mw of a reactive polymer to form a reactive base coat LbL is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, more preferably from about 100,000 Daltons to 5,000,000 Daltons Daltons.

A solution of a reactive polymer to form a reactive base coating LbL on contact lenses can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water miscible organic solvents, an organic solvent, or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent or a mixture of one or more organic solvents. It is believed that a solvent system containing at least one organic solvent can increase the volume of a preformed SiHy contact lens such that a portion of the reactive polymer can penetrate the preformed SiHy contact lens and increase the durability of the coating of reactive base. Any organic solvents described above may be used in the preparation of a solution of the reactive polymer, provided that it can dissolve the reactive polymer.

In another preferred embodiment, a preformed SiHy contact lens inherently comprises amino groups and / or carboxyl groups on and / or near its surface and is further subjected to a surface treatment to form a LbL reactive base coat with groups amino and / or carboxyl groups.

In another preferred embodiment (reactive plasma basecoat), a preformed SiHy contact lens is subjected to a plasma treatment to form a reactive plasma base coat covalently attached on the contact lens, i.e., polymerizing one or more reactive vinyl monomers (any of which has been previously described) under the effect of plasma generated by electric discharge (at 70 ΡΕ 2461767 called plasma-induced polymerization). The term &quot; plasma &quot; indicates an ionized gas, for example, created by discharge of electrical luminescence which may be composed of electrons, ions of one polarity or another, gas atoms and molecules in the soil or any higher state of any form of excitation, as well as photons. It is often called &quot; low temperature plasma &quot;. For a review of plasma polymerization and its uses reference is made to R. Hartmann &quot; Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflächentechnik (1993) 49, pp. 283-296, Battelle-Inst. E.V. Frankfurt / Main Germany; H. Yasuda, &quot; Glow Discharge Polymerization &quot;, Journal of Polymer Science: Macromolecular Reviews, vol. 16 (1981), pp. 199-293; H. Yasuda, &quot; Plasma Polymerization &quot;, Academic Press, Inc. (1985); Frank Jansen &quot; Plasma Deposition Processes &quot;, in Plasma Deposited Thin Films, ed. By T. Mort and F. Jansen, CRC Press Boca Raton (19); O. Auciello et al. (ed.) &quot; Plasma-Surface Interactions and Processing of Materials &quot; publ. by Kluwer Academic Publishers in the NATO ASI Series; Series E: Applied Sciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali &quot; Plasma Polymerization of Selected Organic Compounds &quot;, Polymer, vol. 37 (1996) pp. 333-341. Preferably, the plasma-induced polymerization is a plasma-induced polymerization &quot; after luminescence &quot; as described in WO98028026 (incorporated herein by reference in its entirety). For plasma polymerization &quot; after luminescence &quot; the surface of a contact lens is first treated with a non-polymerizable plasma gas 71 ΡΕ2461767 (for example H2, He or Ar) and then, in a subsequent step, the thus activated surface is exposed to a vinylic monomer having a amino or carboxyl group (any vinyl monomer described above) while the plasma stream has been switched off. Activation results in the plasma induced formation of radicals on the surface which, in the subsequent step, initiate the polymerization of the vinyl monomer thereon.

According to the invention, the water-soluble and crosslinkable hydrophilic polymeric material for forming the hydrogel outer layers (or crosslinked coating) comprises crosslinkable groups, preferably thermally crosslinkable groups, more preferably azetidinium groups. Preferably, the water-soluble and crosslinkable hydrophilic polymeric material to form the hydrogel outer layers (or crosslinked coating) is a partially crosslinked polymeric material comprising a three-dimensional network and crosslinkable (preferably thermally crosslinkable) groups, more preferably azetidinium groups within the network . The term &quot; partially cross-linked &quot; in reference to a polymeric material means that the crosslinkable groups of starting materials to manufacture the polymeric material in the crosslinking reaction have not been completely consumed. Examples of crosslinkable groups include, without limitation, azetidinium groups, epoxy groups, isocyanate groups, aziridine groups, azlactone groups and combinations thereof. 72 ΡΕ2461767

In a preferred embodiment, the water-soluble crosslinkable, hydrophilic polymeric material to form the hydrogel (or crosslinked) outer layers comprises (i) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80% by weight hydrophilic moieties or second polymer chains derived from at least one hydrophilic enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group and combinations thereof, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent bonds, each formed between a azetidinyl group of the polyamine functionalized by epichlorohydrin or polyamidoamine and an amino, carboxy (iii) azetidinium groups which are part of the first polymer chains or pendent or terminal groups covalently attached to the first polymer chains. one

With such a water-soluble crosslinkable hydrophilic polymeric material, the hydrogel (or crosslinked coating) outer layers may be formed by simply heating a preformed SiHi contact lens (having amino and / or carboxyl groups on and / or near the surface of the contact lens, or base coat comprising amino and / or carboxyl groups) in an aqueous solution in the presence of the hydrophilic polymer material up to and at a temperature of about 40 ° C to about 140 ° C for a a period of time sufficient to covalently connect the hydrophilic polymeric material to the contact lens surface through covalent bonds, each formed between an azetidinium group of the hydrophilic polymeric material and one of the amino and / or carboxyl groups on and / or near the surface of the contact lens, thereby forming a cross-linked hydrophilic coating on the contact lens. It is understood that any water-soluble crosslinkable polymeric material containing crosslinkable groups (for example, those described above) may be used in the invention to form the anterior and posterior hydrogel layers of a SiHi contact lens.

A water-soluble, thermally cross-linkable hydrophilic polymeric material comprising (i.e., has a composition comprising) from about 20% to about 95%, preferably from about 35% to about 90%, more preferably from about 50% to about 85% by weight of first polymer chains derived from a polyamine or polyamidoamine functionalized by epichlorohydrin and from about 5% to about 80%, preferably from about 10% to about 65%, still more preferably from about 15% to about 50%, by weight hydrophilic moieties or second polymer chains derived from at least one hydrophilic enhancer agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition (based on the total weight of the reactants) of a reactant mixture used to prepare the thermally crosslinkable hydrophilic polymer material according to the crosslinking reactions set forth in Scheme I above. For example, if a reagent mixture comprises about 75% by weight of an epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of at least one hydrophilicity enhancing agent based on the total weight of the reactants, then the resultant hydrophilic polymeric material comprises about 75% by weight of first polymer chains derived from epichlorohydrin-functionalized polyamine or polyamidoamine and about 25% by weight of hydrophilic moieties or second polymer chains derived from said at least one hydrophilic enhancing agent . The azetidinium groups of the thermally crosslinkable hydrophilic polymeric material are those azetidinium (polyamine or epichlorohydrin functionalized polyamidoamine) groups which do not participate in the crosslinking reactions to prepare the thermally crosslinkable hydrophilic polymeric material.

An epichlorohydrin-functionalized polyamine or polyamidoamine may be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amino groups. For example, a poly (alkylene imines) or a poly (amidoamine) which is a polycondensate derived from a polyamine and a dicarboxylic acid (for example, adipic acid-diethylene triamine copolymers) may be reacted with epichlorohydrin to form a functionalized polymer by epichlorohydrin. Similarly, an aminoalkyl (meth) acrylate homopolymer or copolymer, monoalkylaminoalkyl (meth) acrylate, aminoalkyl (meth) acrylamide, or monoalkylaminoalkyl (meth) acrylamide may also be reacted with epichlorohydrin to form a polyamine functionalized by epichlorohydrin. The reaction conditions for the epichlorohydrin functionalization of a polyamine or polyamidoamine polymer are explained in EP 1465931 (incorporated herein by reference in its entirety). A polymer functionalized by epichlorohydrin is a polyaminoamide epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), such as, for example, Kymene® or Polycup® resins ( epichlorohydrin-functional adipic diethylenetriamine acid copolymers) of Hercules or Polycup® or Servamine® resins from Servo / Delden.

Any suitable hydrophilic enhancers may be used in the invention provided they contain at least one amino group, at least one carboxyl group and / or at least one thiol group. 76 ΡΕ2461767

A preferred class of hydrophilic enhancing agents includes, without limitation: amino, carboxyl or thiol containing monosaccharides (e.g., 3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosaminic acid, mannosamine, saccharic acid, 1,4-lactone, saccharide acid, ketodeoxynonulosonic acid, IV-methyl-D-glucamine, 1-amino-1-deoxy-β-D-galactose, 1-amino- 1-deoxy-sorbitol, 1-methylamino-1-deoxy sorbitol, N-aminoethyl gluconamide); disaccharides containing amino, carboxyl or thiol (for example, sodium chondroitin disaccharide salt, di (β-D-xylopyranosyl) amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionic acid); and amino, carboxyl or thiol containing oligosaccharides (for example, sodium carboxymethyl β-cyclodextrin, trigalacturonic acid); and combinations thereof.

Another preferred class of hydrophilic enhancing agents is that of hydrophilic polymers having one or more amino, carboxyl and / or thiol groups. More preferably, the content in monomeric units having an amino group (-NHR 'with R' as defined above), carboxyl (-COOH) and / or thiol (-SH) in a hydrophilic polymer as a hydrophilic enhancing agent is less than about 40%, preferably less than about 30%, more preferably less than about 20%, even more preferably less than about 10% by weight based on the total weight of the hydrophilic polymer. 77 ΡΕ2461767

A preferred class of hydrophilic polymers as hydrophilic enhancers are those of the amino or carboxyl containing polysaccharides, for example, carboxymethylcellulose (having a carboxyl content of about 40% or less, which is estimated based on the composition of (wherein m is 1 to 3), carboxyethylcellulose (having a carboxyl content of about 36% or less, which is calculated on the basis of the composition of repeating units, - [C6 H10 O- (CH2 Cl2 H) m] (C 2 H 4 CO 2 H) m] in which m is 1 to 3) carboxypropylcellulose (having a carboxyl content of about 32% or less, which is calculated on the basis of the composition of repeat units, - [C 6 H 10 -COO (C 3 H 6 CO 2 H) m] - wherein m is 1 to 3), hyaluronic acid (having a carboxyl content of about 11%, which is calculated on the basis of the composition of repeat units, , chondroitin sulfate (having a carboxyl content of about 9.8%, which is calculated on the base of the composition of repeating units, - (C12 H80 O3 NCO2 H) -), or combinations thereof.

Another preferred class of hydrophilic polymers as hydrophilic enhancers include, without limitation: poly (ethylene glycol) (PEG) with mono-amino, carboxyl group or thiol (e.g., PEG-NH2, PEG-SH, PEG-COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; PEG dendrimers having one or more amino, carboxyl or thiol groups; a diamino or dicarboxyl terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer; a homo- or copolymer terminated by a monoamino or monocarboxyl of a non-reactive hydrophilic vinylic monomer; a copolymer which is a polymerization product of a composition comprising (1) about 60% by weight or less, preferably from about 0.1% to about 30%, more preferably from about 0.5% to about 20%, still more preferably from about 1% to about 15%, by weight of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinylic monomer and / or at least one vinyl monomer containing phosphorylcholine; and combinations thereof. Reactive vinyl monomer (s) and non-reactive hydrophilic vinyl monomer (s) are those previously described.

More preferably, a hydrophilic polymer as the hydrophilic enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; H00C-PEG-C00H; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; dendrimers of PEG with one or more amino, carboxyl or thiol groups; a monoamine, monocarboxyl, diamino or dicarboxyl terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer selected from the group consisting of acrylamide (AAm), N, N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP) , N-vinyl-N-methylacetamide, glycerol (meth) acrylate, hydroxyethyl (meth) acrylate, N-hydroxyethyl (meth) acrylamide, C 1 -C 4 alkoxy-polyethyleneglycol (meth) acrylate having a molecular weight in weighted average of up to 400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl- N, N-dimethylaminoethyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acryloyloxyethyl phosphorylcholine and combinations thereof; a copolymer which is a product of the polymerization of a composition comprising (1) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about about 15% by weight of (meth) acrylic acid, C2-C12 alkylacrylic acid, vinylamine, allylamine and / or (C2 -C4) -alkyl (meth) acryloyloxyethylphosphorylcholine and / or at least a non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N, N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methylacetamide, glycerol (meth) acrylate, hydroxyethyl (meth) acrylate , N-hydroxyethyl (meth) acrylamide; C 1 -C 4 alkoxy-polyethylene glycol (meth) acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol and a combination thereof. Most preferably, the hydrophilicity enhancing agent as a hydrophilicity enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; monoamine, monocarboxyl, diamino or dicarboxyl terminated polyvinylpyrrolidone; monoamino, monocarboxyl, diamino or dicarboxyl terminated polyacrylamide; poly (DMA) terminated by monoamino, monocarboxyl, diamino or dicarboxyl; poly (DMA-co-NVP) terminated by monoamino, monocarboxyl, diamino or dicarboxyl; poly (NVP-co-N, N-dimethylaminoethyl (meth) acrylate) terminated by monoamino, monocarboxyl, diamino or ΡΕ2461767 dicarboxyl; monoamino, monocarboxyl, diamino or dicarboxyl terminated vinyl poly (vinyl alcohol); poly (meth) acryloyloxyethylphosphorylcholine homopolymer or copolymer] terminated by monoamino, monocarboxyl, diamino or dicarboxyl; poly (NVP-co-vinyl alcohol) terminated by monoamino, monocarboxyl, diamino or dicarboxyl; poly (DMA-co-vinyl alcohol) terminated by monoamino, monocarboxyl, diamino or dicarboxyl; poly (meth) acrylic acid-co-acrylamide] with from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15% by weight of (meth) acrylic acid; poly (meth) acrylic acid-co-NVP) with from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15% by weight of (meth) acrylic acid; a copolymer which is a product of the polymerization of a composition comprising (1) (meth) acryloyloxyethylphosphorylcholine and (2) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15%, by weight of a carboxylic acid containing vinyl monomer and / or an amino-containing vinylic monomer, and combinations thereof. PEGs with functional groups and multi-arm functional group PEGs can be obtained from various commercial suppliers, for example, Polyscience and Shearwater Polymers, Inc., etc. 81 ΡΕ2461767

Mono-, monocarboxyl, diamino or dicarboxyl terminated homo- or copolymers of one or more non-reactive hydrophilic vinyl monomers or of a vinyl monomer containing phosphorylcholine may be prepared according to the procedures described in U.S. Patent No. 6,218,508, here incorporated as a reference in its entirety. For example, to prepare a diamino or dicarboxyl terminated homo- or dicarboxyl of a non-reactive hydrophilic vinylic monomer, the non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol , 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptanes, aminomercaptanes or carboxyl-containing mercaptans) and optionally another vinylic monomer are copolymerized (thermally or actinically) with a reactive vinylic monomer (having an amino or carboxyl group ) in the presence of a free radical initiator. Generally, the molar ratio of chain transfer agent to that of all vinylic monomers other than the reactive vinyl monomer is from about 1: 5 to about 1: 100, while the molar ratio of amino or carboxyl chain chain is used to control the molecular weight of the resulting hydrophilic polymer and forms a terminal end of the resulting hydrophilic polymer so as to produce the resulting hydrophilic polymer with an amino or carboxyl end group while the reactive vinyl monomer produces the other carboxyl or amino terminal group to the resulting hydrophilic polymer. 82 ΡΕ2461767

Similarly, to prepare a monoamino or monocarboxyl terminated homo- or monocarboxyl of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer agent having an amino or carboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid, or other hydroxymercaptanes, aminomercaptanes or mercaptans containing carboxyl) and optionally other vinyl monomers are copolymerized (thermally or actinically) in the absence of any reactive vinyl monomer.

As used in this application, a copolymer of a non-reactive hydrophilic vinyl monomer refers to a polymerization product of a non-reactive hydrophilic vinyl monomer with one or more additional vinyl monomers. Copolymers comprising a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (for example, carboxyl-containing vinyl monomer) may be prepared according to any well-known radical polymerization methods or obtained from commercial suppliers. Copolymers containing methacryloyloxyethylphosphoricholine and carboxyl containing vinylic monomer can be obtained from NOP Corporation (e.g., LIPIDURE®-A and -AF). The weight-average molecular weight Mw of the hydrophilic polymer having at least one amino, carboxyl or thiol group (as a hydrophilic enhancing agent) is preferably from about 500 to about 1,000,000 ΡΕ2461767, more preferably from about 1000 to about of 500 000.

According to the invention, the reaction between the hydrophilic enhancing agent and an epichlorohydrin-functionalized polyamine or polyamidoamine is carried out at a temperature of from about 40 ° C to about 100 ° C for a sufficient period of time (from about 0.3 hours to about 24 hours, preferably from about 1 hour to about 12 hours, still more preferably from about 2 hours to about 8 hours) to form a water-soluble thermally cross-linked hydrophilic polymeric material containing azetidinium groups.

According to the invention, the concentration of a hydrophilic enhancing agent relative to an epichlorohydrin-functionalized polyamine or polyamidoamine should be selected not to result in a water-insoluble hydrophilic polymeric material (i.e., a solubility of less than 0.005 g per 100 ml water at room temperature) and not to consume more than about 99%, preferably about 98%, more preferably about 97%, still more preferably about 96% of the azetidinium groups of the polyamine or epichlorohydrin-functionalized polyamidoamine .

According to the invention, heating is preferably effected by autoclaving a preformed contact lens of SiHy 84 and 2441767 comprising amino and / or carboxyl groups on and / or near the surface of the contact lens, or a base coat comprising groups amino and / or carboxyl groups and is immersed in a packaging solution (i.e., a buffered aqueous solution) comprising a water-soluble thermally cross-linkable hydrophilic polymer material in a sealed lens package at a temperature of from about 118 ° C to about 125 ° C for about 20-90 minutes. According to this embodiment of the invention, the packaging solution is an aqueous buffered solution which is ophthalmically safe after autoclaving. Alternatively, it is preferably effected by autoclaving a preformed SiHy contact lens, which comprises a base coat and a layer of a water soluble thermally crosslinkable hydrophilic polymeric material on the base coat, immersed in a packaging solution (i.e. buffered aqueous solution) in a sealed lens package at a temperature of from about 118 ° C to about 125 ° C for about 20-90 minutes.

Lens packs (or containers) are well known to a person skilled in the art for autoclaving and storing a soft contact lens. Any container for lenses may be used in the invention. Preferably, a lens package is a blister pack comprising a base and a cover, wherein the cover is sealed to the base so that it can be withdrawn, wherein the base includes a cavity for receiving a sterile packaging solution and the lens of contact.

The lenses are packaged in individual sealed and sterilized packages (eg by autoclaving at about 120 ° C or more for at least 30 minutes) before being delivered to users. One skilled in the art will understand how to seal and sterilize the lens packs.

According to the invention, a packaging solution contains at least one buffering agent and one or more other ingredients known to a person skilled in the art. Examples of other ingredients include, without limitation, tonicity agents, surfactants, antibacterial agents, preservatives and lubricants (or builders of water-soluble viscosity) (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone). The packaging solution contains a buffering agent sufficient to maintain a pH of the packaging solution in the desired range, for example preferably in a physiologically acceptable range of about 6 to 8.5. Any known, physiologically compatible buffering agents may be used. Buffer agents suitable as constituents of the contact lens care composition according to the invention are known to the person skilled in the art. Examples are: boric acid, borates, for example, sodium borate, citric acid, citrates, for example, potassium citrate, bicarbonates, for example, sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl- 3-propanediol), Bis-Tris (Bis-2-hydroxyethyl-imino-trino (hydroxymethyl) -methane), bis-aminopolyols, triethanolamine, ACES (ε-2-hydroxyethyl) -2-aminoethanesulfonic acid) , BES (N, N-Bis (2-hydroxyethyl) -2-aminoethanesulfonic acid), HEPES (4- (2-hydroxyethyl) -1-piperazinoethanesulfonic acid, MES (2- (N-morpholino) ethanesulfonic acid (N-N-bis (2-ethanesulfonic acid), TES (N- [Tris (hydroxymethyl) methyl] -2-methyl-propionic acid), MOPS (3- [N-morpholino] propanesulfonic acid) A preferred bis-aminopolyol is 1,3-bis (tris [hydroxymethyl] -methylamino) propane (bis-TRIS-propane), and the like, ) The amount of each buffer in a solution of packaging is preferably from 0.001% to 2%, preferably from 0.01% to 1%; and most preferably from about 0.05 to about 0.30% by weight. The packaging solution has a tonicity of from about 200 to about 450 milliosmoles (mOsm), preferably from about 250 to about 350 mOsm. The tonicity of a packaging solution can be adjusted by the addition of organic or inorganic substances that affect tonicity. Suitable ocular tonicity agents include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitols, sorbitol, xylitol and mixtures thereof. 87 ΡΕ2461767

A packaging solution of the invention has a viscosity of from about 1 centipoise to about 20 centipoises, preferably from about 1.2 centipoises to about 10 centipoises, more preferably from about 1.5 centipoises to about 5 centipoises, 25 ° C.

In a preferred embodiment, the packaging solution preferably comprises from about 0.01% to about 2%, more preferably from about 0.05% to about 1.5%, still more preferably from about 0.01% 1% to about 1%, most preferably from about 0.2% to about 0.5%, by weight of a thermally crosslinkable, water-soluble hydrophilic polymeric material of the invention.

A packaging solution of the invention may contain a viscosity enhancing polymer. The viscosity enhancing polymer is preferably nonionic. Increasing the viscosity of the solution produces a film on the lens that can facilitate the comfortable use of the contact lens. The viscosity enhancing component may also act to cushion the impact on the surface of the eye during insertion and also serves to alleviate eye irritation.

Viscosity-enhancing polymers include, but are not limited to, water-soluble cellulose ethers (e.g., methylcellulose (MC), ethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), or a mixture thereof), water-soluble polyvinyl alcohols (PVAs), high molecular weight poly (ethylene oxide) having a molecular weight greater than about 2000 (up to 10,000,000 Daltons), polyvinylpyrrolidone having a molecular weight from about from 30,000 daltons to about 1,000,000 daltons, a copolymer of N-vinylpyrrolidone and at least one dialkylaminoalkyl (meth) acrylate (with 7-20 carbon atoms and combinations thereof) The most preferred viscosity enhancing polymers are ethers cellulosic copolymers and the copolymers of water-soluble dimethylaminoethyl vinylpyrrolidone and methacrylate The copolymers of N-vinylpyrrolidone and dimethylamino methacrylate Copolymer 845 and ISOL Copolymer 937 are available commercially. The viscosity-potentiating polymer is present in the packaging solution in an amount of from about 0.01% to about 5% by weight, preferably from about 0.05% to about 3% by weight, even more preferably from about 0.1% to about 1% by weight, based on the total amount of the packaging solution.

A packaging solution may further comprise a polyethylene glycol having a molecular weight of about 1200 or less, more preferably 600 or less, most preferably from about 100 to about 500

Daltons. 89 ΡΕ2461767

Where at least one of the crosslinked coating and the packaging solution contains a polymeric material with polyethylene glycol segments, the packaging solution preferably comprises a cx-oxo-multi-acid or salt thereof in an amount sufficient to have a low susceptibility to degradation by oxidation of the polyethylene glycol segments. A common proprietary and co-pending patent application (U.S. Patent Application Publication No. 2004/0116564 A1, incorporated herein in its entirety) discloses that the oxo-multi-acid or salt thereof may reduce the susceptibility to oxidative degradation of a polymer material containing PEG. Exemplary α-Οχο · -multi-acids or biocompatible salts thereof include, without limitation, citric acid, 2-ketoglutaric acid, or malic acid or biocompatible (preferably ophthalmically compatible) salts thereof. Most preferably, an α-oxo-multi-acid is citric or malic acid or biocompatible (preferably ophthalmically compatible) salts thereof (e.g., sodium, potassium, or the like).

According to the invention, the packaging solution may further comprise materials of the mucin type, ophthalmically beneficial materials and / or surfactants. The exemplary mucin-like materials described above, exemplary ophthalmically beneficial materials described above, exemplary surfactants described above may be used in this embodiment. 90 ΡΕ2461767

In a preferred embodiment, a SiHy contact lens of the invention has a relatively long water-break time (WBUT). WBUT is the time required for the water film to rupture (dehumidify) by exposing the underlying lens material to the visual examination. A SiHy contact lens with a longer WBUT can maintain a water film (tears) on its surface for a relatively longer period when used in the eye. It would be less likely to develop dry areas between the blink of the eyelids and could enhance comfort in use. The WBUT can be measured according to the procedures described in the following Example. Preferably, a SiHy contact lens of the invention has a hydrophilic surface characterized by having a water break time of at least about 10 seconds.

In a preferred embodiment, a SiHy contact lens of the invention has a surface wetting characterized by having a mean water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, still more preferably about 60 degrees or less, most preferably about 50 degrees or less.

In a preferred embodiment, a SiHy contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, still more preferably at least about 100, preferably at least about 100. more preferably at least about 120 barrers / mm.

It is to be understood that although in this aspect of the invention various embodiments, including preferred embodiments of the invention, may be separately described above, may be combined and / or used together in any desirable manner to achieve different embodiments of a silicone hydrogel contact lens of the invention.

In another aspect, the invention produces a silicone hydrogel hydrated contact lens. A silicone hydrogel hydride contact lens of the invention comprises: a silicone hydrogel material as the mass matter, a front surface and an opposing rear surface; wherein the contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, still more preferably at least about 110 barrers / mm, and a profile of the a cutting surface comprising, along a shorter line between the anterior and posterior surfaces on the surface of a cut of the contact lens, an anterior outer zone including and close to the anterior surface, an inner zone including and about the center of the the shorter line and a rearward outer zone including the and near the rear surface, wherein the front outer zone has a mean anterior surface modulus (designated SMAnt) while the posterior outer zone has a median posterior surface module (designated by SMPost), where the inner zone has an average inner surface module (called SMInner), where

at least one of SMfraw &quot; SM beutr

KJ

WK5C is at least about 20%, preferably at least about 25%, more preferably at least about 30%, still more preferably at least about 35%, most preferably at least about 40%. Preferably, the anterior and posterior exterior zones cover a range of at least about 0.1 Âμm, preferably from about 0.1 Âμm to about 20 Âμm, more preferably from about 0.25 Âμm to about 15 Âμm, still more preferably from about 0.5 Âμm to about 12.5 Âμm, most preferably from about 1 Âμm to about 10 Âμm.

In a preferred embodiment, the silicone hydrogel hydrated contact lens may have an elastic modulus (or Young's Modulus) from about 0.3 MPa to about 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa; a water content of from about 10% to about 75%, preferably from about 10% to about 70%, more preferably from about 15% to about 65%; and more preferably from about 20% to about 60%, most preferably from about 93% to about 24% by weight; a surface wetting characterized by having a mean water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, still more preferably about 60 degrees or less, more preferably about 50 degrees or less; a surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or combinations thereof.

In another preferred embodiment, the front and back surfaces have a reduced surface concentration of negatively charged groups (for example, carboxylic acid groups) such as characterized in that they attract at most about 200, preferably at most about 160, more preferably at least to about 120, most preferably at most about 90, most preferably at most about 60 positively charged particles in a positively charged particulate adhesion test. To have a reduced surface concentration of negatively charged groups (for example, carboxylic acid groups), the hydrogel front and back outer layers should have a relatively low carboxylic acid content. Preferably, the hydrogel anterior and posterior outer layers have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, still more preferably about 10% 94 ΡΕ2461767 by weight or less, most preferably about 5% by weight or less.

In another preferred embodiment, a SiHy contact lens of the invention has good surface lubrication characterized by having a critical coefficient of friction (designated CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, a SiHy contact lens of the invention preferably has better lubrication than the ACUVUE OASYS or ACUVUE TruEye as measured in a blind test in accordance with the lubrication assessment procedures described in Example 1.

In another preferred embodiment, the hydrated SiHy contact lens preferably has a high digital friction resistance such as characterized in that it does not have visible surface cracking lines under a dark field after the SiHy contact lens has been rubbed between the fingers . It is believed that surface cracks induced by digital friction can reduce surface lubrication and / or may not be able to prevent the silicone from migrating onto the surface (exposure).

In a further preferred embodiment, a hydrated SiHi contact lens of the invention comprises an inner layer of the silicone hydrogel materials, a hydrogel anterior outer layer and a hydrogel rear outer layer, wherein the outer, anterior and posterior layers, hydrogels have a substantially uniform thickness and fuse at the peripheral edge of the contact lens to completely enclose the inner layer of the silicone hydrogel material. It will be understood that the first and second zones in the profile of the cut surface module correspond to the two hydrogel outer layers while the inner zone corresponds to the inner layer of the silicone hydrogel material. All of the various embodiments of the hydrogel outer layers (crosslinked coating) as described above for the other aspect of the invention may be used alone or in any combination in this aspect of the invention as the outer layers in hydrogel. All of the various embodiments of the inner layer of a silicone hydrogel material as described above for the other aspects of the invention may be used alone or in any combination in this aspect of the invention as the inner layer of the silicone hydrogel material.

According to this aspect of the invention, the hydrogel outer layers have a substantially uniform thickness and have a thickness of at least about 0.1 Âμm, preferably from about 0.1 Âμm to about 20 Âμm, more preferably from about from about 0.25 Âμm to about 15 Âμm, still more preferably from about 0.5 Âμm to about 12.5 Âμm, most preferably from about 1 Âμm to about 10 Âμm. The thickness of each 96 ΡΕ2461767 hydrogel outer layer of a SiHy contact lens of the invention is determined by AFM analysis of a severely hydrated state SiHy contact lens cut as described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably about 10% (10% or less) of the thickness of the center of the contact lens SiHy in a fully hydrated state. Further, each of the two hydrogel outer layers is substantially free of silicone (as characterized by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, still more preferably about 3% or less, of the total elemental percentage as measured by XPS analysis of the contact lens in the dry state), preferably completely free of silicone. It will be understood that a small percentage of silicone may optionally (but not preferably) be incorporated into the polymer network of the hydrogel outer layer so long as it does not significantly detract from the surface properties (hydrophilicity, wetting and / or lubrication) of a SiHy contact.

In another preferred embodiment, the two hydrogel outer layers of a SiHy hydrated contact lens of the invention comprise a water content greater than the water content (designated WCLens) of the silicone hydrogel hydrated contact lens and, moreover, 97 Specifically, it should be at least about 1.2 times (i.e., 120%) WCLens. It is believed that the ratio of volume increase per water of each outer layer to hydrogel may represent approximately the water content of outer hydrogel layer as discussed above. Where WCLens is about 45% or less, the ratio of volume increase per water of each outer layer to hydrogel is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, even more preferably at least about 300%. Where WCLens is greater than 45%, the ratio of volume increase per water of each outer layer to hydrogel is at least about

preferably about

In most preferred embodiments, where WCLens is about 55% or less, in preferred embodiments, wherein WCLs are about 55% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 150%, where WCLens is about 60% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 200%, where WCLens is about 65% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 250%, where WCLens is about 70% % or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 300%.

Preferably, the contact lens SiHy further comprises a transition layer located between the silicone hydrogel material and the hydrogel outer layer. All of the various embodiments of the transition layer, as described for the foregoing aspect of the invention, may be used, alone or in any combination, in this aspect of the invention.

A hydrated SiHy contact lens of the invention may be prepared according to the methods described above. All of the various embodiments of the inner layer (i.e., silicone hydrogel material) described above may be used, alone or in any combination, in this aspect of the invention as the silicone hydrogel core. All of the various embodiments described above for the prior aspect of the invention may be used, alone or in any combination, in this aspect of the invention.

It is to be understood that, although in this aspect of the invention various embodiments, including preferred embodiments of the invention, may be described separately, may be combined and / or used together in any desirable manner to arrive at different embodiments of silicone hydrogel contact lenses of the invention. All of the various embodiments described above for the prior aspect of the invention may be used alone or in combination in any manner desirable in this aspect of the invention.

In another aspect, the invention provides a silicone hydrogel hydrated contact lens. A silicone hydrogel hydride contact lens of the invention comprises: a silicone hydrogel material as the mass matter, a front surface and an opposing rear surface; when the contact lens has (1) an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, still more preferably at least about 110 barrers / mm, and (2 ) a surface lubrication characterized by having a critical coefficient of friction (referred to as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and back surfaces have a surface concentration reduced groups of negatively charged groups including carboxylic acid groups as characterized in that they attract at most about 200, preferably at most about 160, more preferably at most about 120, still more preferably at most about 90, most preferably at most about 60 positively charged particles in a positively charged particulate adherence test. 100 ΡΕ2461767

In a preferred embodiment, the silicone hydrogel hydrated contact lens has an elastic modulus (or Young's Modulus) of from about 0.3 MPa to about 1.8 MPa, preferably from about 0.4 MPa to about of 1.5 MPa, more preferably from about 0.5 MPA to about 1.2 MPa; a water content of from about 10% to about 75%, preferably from about 10% to about 70%, more preferably from about 15% to about 65%, still more preferably from about 20% to about of 60%, most preferably from about 25% to about 55% by weight; a surface wetting characterized by having a water contact angle of on average 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, still more preferably about 60 degrees or less, the highest preferably about 50 degrees or less; a surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or combinations thereof.

In another preferred embodiment, the hydrated SiHy contact lens preferably has a high resistance to digital friction as characterized by not having visible surface lines of cleft under a dark field after a contact lens SiHy is rubbed between the fingers . It is believed that surface cracks induced by digital friction can reduce surface lubrication and / or may not be able to prevent the silicone from migrating onto the surface (exposure). 101 ΡΕ2461767

In a further preferred embodiment, a hydrated SiHy contact lens of the invention comprises an inner layer of the silicone hydrogel material, a hydrogel anterior outer layer and a hydrogel posterior outer layer, wherein the outer, anterior and posterior hydrogel layers have a substantially uniform thickness and fuse at the peripheral edge of the contact lens to completely enclose the inner layer of the silicone hydrogel material. It will be understood that the first and second outer zones in the profile of the cut surface module correspond to the two outer layers in hydrogel while the inner zone corresponds to the inner layer of the silicone hydrogel material. All of the various embodiments of the hydrogel outer layers (crosslinked coating), as described above for the other aspect of the invention, may be used, alone or in any combination, in this aspect of the invention, as the outer layers in hydrogel . All of the various embodiments of the inner layer of a silicone hydrogel material as described above for the other aspect of the invention may be used alone or in any combination in this aspect of the invention as the inner layer of the material in silicone hydrogel.

According to this aspect of the invention, the hydrogel outer layers have a substantially uniform thickness and have a thickness of at least about 0.1 Âμm, preferably from about 0.1 Âμm to about 20 Âμm, more preferably from about from 0.25 Âμm 102 Â ± 24241767 to about 15 Âμm, even more preferably from about 0.5 Âμm to about 12.5 Âμm, most preferably from about 1 Âμm to about 10 Âμm. The thickness of each outer hydrogel layer of a SiHy contact lens of the invention is determined by AFM analysis of a cut of the SiHy contact lens in a fully hydrated state as described above. In a more preferred embodiment, the thickness of each outer layer in hydrogel is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably at most about 10% (10% or less) of the central thickness of the SiHy contact lens in a fully hydrated state. Further, each of the two hydrogel outer layers is substantially free of silicone (as characterized by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, still more preferably about 3% or less, of the total elemental percentage, as measured by XPS analysis of the contact lens in the dry state), preferably completely free of silicone. It will be understood that a small percentage of silicone may optionally (but not preferably) be incorporated into the polymer network of the hydrogel outer layer so long as it does not significantly detract from the surface properties (hydrophilicity, wetting and / or lubrication) of a SiHy contact. In order to have a reduced surface concentration in negatively charged groups (for example, carboxylic acid groups), the outer layers, in front and rear, in hydrogels should have a relatively reduced carboxylic acid content. Preferably, the hydrogel front and back outer layers have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, still more preferably about 10% by weight or less, the more preferably about 5% by weight or less.

In another preferred embodiment, the two hydrogel outer layers of a hydrated SiHy contact lens of the invention comprise a water content greater than the water content (designated WCLens) of the silicone hydrogel hydrated contact lens and, more specifically, should be at least about 1.2 times (i.e., 120%) of the water content (WCLens) of the silicone hydrogel contact lens. It is believed that the ratio of volume increase per water of each outer layer to hydrogel may roughly represent the water content of the outer hydrogel layer as discussed above. When WCLens is about 45% or less, the ratio of volume increase per water of each outer layer to hydrogel is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250%, still more preferably at least about 300%. When WC Lens is greater than 45%, the ratio of volume increase per water of each outer layer to hydrogel is at least about 104 ΡΕ2461767 of

preferably about 130Â ° C, more preferably about 30Â ° C.

140 * Toilet even more

1-WC

Preferably about 1.5% WCt4fS In alternatively preferred reaction models, when WCLens is about 55% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 150%; when WCLens is about 60% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 200%; when WCLens is about 65% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 250%; when WCLens is about 70% or less, the ratio of volume increase per water of each outer layer to hydrogel is at least about 300%.

In another preferred embodiment, the hydrogel outer and back layers independent of each other have a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, still more preferably at least about 35%, most preferably at least about 40%, relative to the inner layer.

Preferably the contact lens SiH1 105 ΡΕ2461767 further comprises a transition layer located between the silicone hydrogel material and the outer hydrogel layer. All of the various transition layer embodiments may be used, as described for the prior aspect of the invention, by itself or in any combination, in this aspect of the invention.

A hydrated SiHy contact lens of the invention may be prepared according to the methods described above. All of the various embodiments of the inner layer (i.e., silicone hydrogel material) described above may be used, alone or in any combination, in this aspect of the invention, as the silicone hydrogel core. All of the various embodiments, as described above for the prior aspect of the invention, by itself or in any combination, may be used in this aspect of the invention.

It is to be understood that, although in this aspect of the invention various embodiments, including preferred embodiments of the invention, may be described separately, may be combined and / or used together in any desirable manner to arrive at different embodiments of silicone hydrogel contact lenses of the invention. All of the various embodiments described above for the prior aspect of the invention may be used alone or in combination in any manner desirable in this aspect of the invention. The prior disclosure will enable one of ordinary skill in the art to practice the invention. Various modifications, variations and combinations may be made to the various embodiments described herein. To enable the reader to better understand the specific embodiments and their advantages, reference is made to the following examples. It is intended that the description and the examples be considered exemplary.

While various aspects and various embodiments of the invention have been described using specific terms, devices and methods, such disclosure serves only an illustrative purpose. The words used are words of description and not of limitation.

Example 1

Measurements of Oxygen Permeability The apparent oxygen permeability of a lens and the transmissibility of oxygen in a lens material determined according to a technique similar to that described in U.S. Patent No. 5,760,100 and in an article by Winterton et al. (The Cornea: Transactions of the World Congress on Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp. 273-280), both of which are hereby incorporated by reference in their entirety. Oxygen flows (J) are measured at 34øC in a wet cell (ie 107 Å 246 1767, ie the gas streams are maintained at about 100% relative humidity) using a DklOOO instrument (available from Applied Design and Development Co. , Norcross, GA), or similar analytical instrument. A stream of air having a known oxygen percentage (e.g., 21%) is passed through one side of the lens at a rate of about 10 to 20 cm 3 / min, while a stream of nitrogen passes through the opposite side of the lens at a rate of about 10 to 20 cm 3 / min. A sample is equilibrated in a test medium (i.e., saline or distilled water) at the prescribed test temperature for at least 30 minutes prior to measurement but not more than 45 minutes.

Any test medium used as a overlay is equilibrated at the prescribed test temperature for at least 30 minutes prior to measurement but not more than 45 minutes. The speed of the agitator motor is set to 1200 + 50 rpm, corresponding to an indicated mark of 400.times.155 in the stepper motor controller. The barometric pressure surrounding the system, measured, is measured. The thickness (t) of the lens in the area exposed to tests is determined by measuring about 10 sites with a Mitotoya VL-50 micrometer, or similar instrument, and averaging the measurements. The concentration of oxygen in the stream of nitrogen (i.e., oxygen diffusing through the lens) is measured using the DK1000 instrument. The apparent oxygen permeability of the lens material, DKapp, is determined from the following formula:

108 ΡΕ2461767 where J = oxygen flow [microlithes 02 / cm2-min]

Pozz = = (Pme = P2 = in air current) [mm Hg] = partial pressure of oxygen in the air stream

(Mm Hg) = Average Hg at 40 ° C (in a wet cell) (mm Hg) t = Mean thickness of the lens (mm Hg) in the exposed test area (mm)

Dkapp is expressed in units of barrers. The apparent oxygen transmissibility (Dk / t) of the material can be calculated by dividing the apparent oxygen permeability (Dkapp) by the average thickness (t) of the lens.

The above-described measurements are not corrected for the so-called boundary layer effect which is attributable to the use of a water bath or saline solution at the top of the contact lens during measurement of the oxygen flow. The boundary layer effect causes the reported value so that the apparent Dk of a silicone hydrogel material 109 ΡΕ2461767 is lower than the current intrinsic Dk value. In addition, the relative impact of the boundary layer effect is superior for lenses thinner than for thicker lenses. The net effect is that the reported Dk seems to change as a function of the thickness of the lens when it should be kept constant. The intrinsic value Dk of a lens can be calculated as follows, based on a corrected Dk value for the surface resistance up to the oxygen flow caused by the boundary layer effect.

Measure the apparent oxygen permeability values (single point) of the reference lotrafilcon A (Focus® N &amp; D® from CIBA VISION CORPORATION) or lotrafilcon B (AirOptix ™ from CIBA VISION CORPORATION) using the same equipment. The reference lenses have an optical power similar to that of the test lenses and are measured concurrently with the test lenses.

Measure the oxygen flow through a series of thicknesses of the lotrafilcon A or lotrafilcon B (reference) lenses using the same apparatus according to the procedure for apparent measurements of Dk described above, to obtain the intrinsic value of Dk (Dkj. ) of the reference lens. A series of thicknesses should cover a thickness range of approximately 100 μm or more. Preferably, the thickness range of the reference lenses will encompass the thicknesses of the test lenses. 110 ΡΕ2461767

Dkapp of these reference lenses should be measured on the same equipment as the test lenses and should ideally be measured contemporaneously with the test lenses. The preparation of the equipment and the measurement parameters must be kept constant throughout the experiment. Individual samples can be measured multiple times, if desired.

Determine the residual oxygen resistance value, Rr, from the reference lens results using equation 1 in the calculations.

fi)

Where t is the thickness of the test lens (i.e., also the reference lens), and n is the number of measured reference lenses. Mark the residual oxygen resistance value, Rr, against the data of t and draw a curve of the form Y = a + bX where, for the lens j, Yj = (ÁP / J) j and X = tj. The residual oxygen resistance, Rr is equal to a.

Use the residual oxygen resistance value determined above to calculate the correct oxygen permeability Dkc (calculated intrinsic Dk) for the test lenses based on Equation 2. 111 ΡΕ2461767

Dke «URt / CM-Rii (2) The calculated intrinsic Dk of the test lenses can be used to calculate what would have been the apparent Dk (Dka-std) for a standard thickness lens in the same test environment based on Equation 3. The Standard Thickness (tstd) for lotrafilcon A = 85 Âμm. The thickness

Standard for lotrafilcon B = 60 pm. DKjm * w K W DM + m

Measurement of Ion Permeability The ionic permeability of a lens is measured according to processes described in U.S. Patent No. 5,760,100 (incorporated herein by reference in its entirety. The ion permeability values reported in the following examples are relative ionofluor diffusion coefficients (D / Dref) with reference to a lens material, Alsacon, as reference material. Alsacon has an ionophilic diffusion coefficient of 0.314 x 10-3 mm2 / min.

Lubrication Rating Lubrication qualification is a qualitative classification scheme where 0 is attributed to the control of lenses coated with polyacrylic acid, 1 is assigned to 112 ΡΕ2461767 commercial lenses Oasys ™ / TruEye ™ and 4 is assigned to commercial Air Optix ™ lenses. Samples are washed with excess Di water for at least three times and then transferred to PBS prior to evaluation. Prior to evaluation, the hands are washed with a soap solution, extensively rinsed with DI water and then dried with KimWipe® towels. Samples are handled between the fingers and a numerical number is assigned to each sample relative to the above standard lenses. For example, if the lenses are determined to be only slightly better than Air Optix ™ lenses, then they are assigned a number 3. For consistency purposes, all qualifications are independently collected by the same two operators to avoid deviations and qualitative agreement and consistency in assessment.

Surface Wetness Testing. The contact angle with the water in a contact lens is a general measure of the surface wetting of the contact lens. In particular, a reduced water contact angle corresponds to a larger wettable surface. The average contact (Sésil Drop) angles of the contact lenses are measured using a VCA 2500 XE contact angle metering device from AST, Inc., located in Boston, Massachusetts. This equipment is capable of measuring advanced or recessed contact angles or sessile (static) contact angles. Measurements are made on fully hydrated contact lenses and immediately after blotting drying as follows. A contacting 113 ΡΕ2461767 lens is removed from the vial and washed 3 times in ~ 200 ml of fresh Di water to remove the packaging additives which are slightly retained therein from the lens surface. The lens is then placed on a clean cotton-free cloth (Alpha Wipe TX1009), well-buffed to remove water from the surface, mounted on a contact angle measuring pedestal, dried with a blow of dry air, and finally the angle of contact of the sessile drop is automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity &gt; ΙδΜΩαη and the droplet volume used is 2μl. Typically, silicone hydrogel lenses (after autoclaving) have a sessile drop contact angle of about 120 degrees. The tongs and pedestal are thoroughly washed with isopropanol and washed with DI water before contacting the contact lenses.

Water Breakage Testing (WBUT). The hydrophilicity of the lens surface (after autoclaving) is evaluated by determining the time required for the water film to begin to fail at the lens surface. Briefly, the lenses are removed from the vial and washed 3 times in 200 ml of fresh DI water to remove the packaging additives which have been slightly retained therein from the surface of the lens. The lens is removed from the solution and held with tweezers against a bright light source. The time it is necessary for the water film to break (dehumidify) by exposing the underlying lens material is noted visually. Uncoated lenses 114 ΡΕ2461767 instantly rupture upon removal from the water D1 and are assigned a WBUT of 0 seconds. Lenses exhibiting a WBUT of &gt; 5 seconds are considered to have good hydrophilicity and are expected to exhibit adequate capacity to support the tear film in the eye.

Intact Coating Tests. The ability of a coating to remain intact on the surface of a contact lens can be tested according to the Sudan Black Stain test as follows. Contact lenses with a coating (a LbL coating, a plasma coating or any other coatings) are dipped in a solution of Sudan Black dye (Sudan Black in vitamin E oil) and are then rinsed extensively in water. Sudan Black dye is hydrophobic and has a great tendency to be absorbed by a hydrophobic material or on a hydrophobic lens surface or hydrophobic stains on a surface partially coated with a hydrophobic lens (for example, silicone hydrogel contact lenses). If the coating on a hydrophobic lens is intact, spot spots on the or the lens should not be observed. All lenses under test are fully hydrated.

Coating durability tests. The lenses are digitally rubbed with Sol-care® multifunction lens care solution for 30 times and then washed with saline solution. The process described above is repeated a number of times, for example, from 1 115 ΡΕ 2461767 to 30 times (i.e., number of consecutive digital friction tests mimicking cleansing and dipping cycles in the liquid). The lenses are then subjected to the Sudan Black test (i.e., the intact coating test described above) to examine whether the coating is still intact. To survive the digital friction test there is no significant increase in stain spots (for example, spot spots covering no more than about 5% of the total surface of the lens). The angles of contact with water are measured to determine the durability of the coating.

Determination of azetidinium content. The azetidin content in PAE can be determined according to one of the following tests.

PPV assays. The charge density of the PAE (i.e. the azetidinium content) may be determined according to the PPVS assay, a colorimetric titration assay where the titrated solution is potassiumsulfanylsulfate (PPVS) and the indicator is Toluidine Blue. See S-K Kam and J. Gregory, &quot; Charge determination of synthetic cationic polyelectrolytes by colloid titration &quot;, in Collold &amp; Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds to the positively charged species, for example, Toluidine Blue and the azetidinium groups of PAE. Decreases in the absorbency intensities of Toluidine Blue are indicative of the density of the proportional charge of the PAE (azetidin content). 116 ΡΕ2461767

PES-Na Assay. The PES-Na assay is another colorimetric titration assay to determine the PAE (azetidinium content) charge density. In this test, the titrated solution is sodium polyethylenesulfonate (PES-Na) instead of PPVS. The assay is identical to the PPVS assay described above.

PCD assays. The PCD assay is a potentiometric titration assay to determine the charge density of the PAE (azetidinium content). The titrated solution is sodium polyethylenesulfonate (PES-Na), PPVS or the like. The PAE charge is detected by an electrode, for example, using the BTD Miitek PCD-04 Particle Charge Detector. The principle of measuring this detector can be found on BTG's website http://www.bbg.com/pro-ducts.asp?langage=l&amp;appli=5&amp;numProd=357&amp;cat=prod). NMR method. The positively charged portion active in the PAE is the azetidinium (AZR) group. The NMR ratio method is a ratio of the number of protons specific per AZR group against the number of non-AZR related protons. This ratio is an indicator of the AZR charge or density for PAE.

Debris Adhesion Test. Contact lenses with a highly loaded surface may be susceptible to increased adherence of debris during handling by the patient. A paper towel is rubbed against gloved hands and then both sides 117 ΡΕ2461767 of the lens are rubbed with the fingers to transfer any debris to the surface of the lens. The lens is briefly washed and then observed under a microscope. A qualitative rating scale from 0 (no debris adherence) to 4 (debris adherence equivalent to a PAA-coated control lens) is used to classify each lens. Lenses with a score of &quot; 0 &quot; or &quot; 1 &quot; are considered acceptable.

Example 2

Preparation of the CE-PDMS Macromer

In the first step, α-bis (2-hydroxyethoxypropyl) polydimethylsiloxane (Mn = 2000, Shin-Etsu, Kf-6001a) is capped with isophorone diisocyanate (IPDI) by the reaction of 49.85 g of α, (2-hydroxyethoxypropyl) polydimethylsiloxane with 11.1 g of IPDI in 150 g of methyl methylethylketone (MEK) in the presence of 0.063 g of dibutylstannyl dilaurate (DBTDL). The reaction is maintained for 4.5 h at 40øC, forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α, CO-bis (2-hydroxyethoxypropyl) polydimethylsiloxane (Mn = 3000, Shin-Etsu, KF-6002) and 50 g of dry MEK are added dropwise to the solution of IPDI-PDMS-IPDI to which a further 0.063 g of DBTDL was added. The reactor is maintained for 4.5 h at about 40øC, forming HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. The MEK is then removed under reduced pressure. In the third step, the terminal hydroxyl groups are capped with methacryloyloxyethyl groups in a third step by adding 7.77 g of isocyanatoethyl methacrylate (IEM) and 118 ΡΕ2461767 plus 0.063 g of DBTDL, forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS- IEM (ie, CE-PDMS terminated with methacrylate groups).

Alternative Preparation of CE-PDMS Macromer with Methacrylate Terminal Groups

240.43 g of KF-6001 is added to a 1-L reactor equipped with stirring, thermometer, cryostat, bromine ampoule and nitrogen valve / vacuum inlet adapter and is then dried by high vacuum ( 2x10-2 mbar). Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK are then added to the reactor and the mixture is thoroughly stirred. 0.235 g of DBTDL is added to the reactor. After the reactor is heated to 45øC, 45.86 g of IPDI are added to the reactor via a bromine funnel for 10 minutes under moderate agitation. The reaction is maintained for 2 hours at 60 ° C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are then added and stirred until a homogeneous solution is formed. About 0.235 g of DBTDL are added and the reactor is maintained at about 55øC overnight under a blanket of dry nitrogen. The next day the MEK is removed by spark distillation. The reactor is cooled and 22.7 g of EMI are then charged into the reactor followed by about 0.235 g of DBTDL. After about 3 hours, an additional 3.3 g of EMI is added and the reaction is allowed to proceed overnight. The next day, the reaction mixture is cooled to about 18 ° C to obtain the EC-PDMS macromer with methacrylate terminal groups 119 ΡΕ2461767.

Example 3

Preparation of Formulations for Lenses

A lens formulation is prepared by dissolving the components in 1-propanol to have the following composition: 33% by weight of EC-PDMS macromer prepared in Example 2, 17% by weight N- [tris (trimethylsiloxy) silylpropyl] acrylamide (TRIS-Am), 24% by weight of N, N-dimethylacrylamide (DMA), 0.5% by weight of N- (carbonylmethoxypolyethyleneglycol-2000) -1,2-disteloyl-sn-glycero-3-phosphoethanolamine , sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of visitint (5% dispersion of phthalocyanine blue pigment in tris (tri-methylsiloxy) silylpropylmethacrylate , TRIS) and 24.5% by weight of 1-propanol.

Lens Preparation

The lenses are prepared by cast molding from the lens formulation back prepared in a reusable mold, similar to the mold shown in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6). The mold comprises a female mold half made of CaF2 and a male mold half made of PMMA. The UV irradiation source is a Hamamatsu lamp with the cut filter WG335 + TM297 at an intensity of about 4 mW / cm2. The lens formulation in the template is 120 ΡΕ2461767 irradiated with UV irradiation for about 25 seconds. The cast cast lenses are extracted with water-washed, polyacrylic acid (PAA) -coated isopropanol (or methylethylketone, MEK), by immersing the lenses in a 10% by weight PAA-propanol solution acidified with formic acid to about pH 2.5), and hydrated in water. The resulting lenses having a PAA-LbL over reactive base coating are determined to have the following properties: ion permeability of about 8.0 to about 9.0 relative to the Alsacon lens material; Apparent Dk (single point) of about 90 to 100; a water content of about 30% to about 33%; and an elastic modulus of the mass of about 0.60 MPa to about 0.65 MPa.

Example 4

A saline solution for indoor plating (IPC) is prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE) (Kymene from Ashland as an aqueous solution and used as received, 0.46 azetidin content assayed with NMR) in phosphate buffered saline (PBS, hereinafter) (about 0.044 w / w% NaH 2 PO 4 .H 2 O, about 0.388 w / w% Na 2 HPO 4 .2H 2 O, about 0.79 w / w% NaCl), and the pH is then adjusted to 7.2-7.4.

The lenses of Example 3 are placed in a polypropylene liner packaging shell with 0.6 ml of IPC saline (half of the IPC saline solution is 121 ΡΕ 2461767 added before inserting the lens). The blister is then sealed with metal film and autoclaved for about 30 minutes at 121 ° C, forming crosslinked coatings (PAA-x-PAE coating) on the lenses.

Therefore, the lenses are evaluated in terms of debris adhesion, surface cracking, lubrication, contact angle and water breaking time (WBUT). The test lenses (packaged / autoclaved in IPC saline solution, i.e. PAA-x-PAE coated lenses on top) do not exhibit debris adherence after being rubbed against a paper towel while the control lenses (packaged / autoclaved in PBS, i.e., PAA-LbL base coat lenses on top) show severe adherence of debris. The water contact angle (WCA) of the test lenses is reduced (-20 degrees) but the WBUT is less than 2 seconds. When observed under the darkfield microscope, several lines of cracking are visible after the lens is handled (lens inversion and friction between the fingers). The test lenses are much less lubricated than the control lenses, as judged by a qualitative friction test between the fingers.

Example 5

Partial sodium salt of poly (acrylamido-co-acrylic acid) (or PAAm-PAA or poly (AAm-co-AA) or p (AAm-co-AA)) (-80% solids, -AA) (80/20), Mw. 520 000, 122 ΡΕ2461767 Μη 150 000) is purchased from Aldrich and used as received.

An IPC salt solution is prepared by dissolving 0.02% Poly (AAm-co-AA) (80/20) and 0.2% PAE (Kymene from Ashland as aqueous solution and used as received, azetidin content of 0 , Assayed with NMR) in PBS. The pH is adjusted to 7.2-7.4. PBS is prepared by dissolving 0.76% NaCl, 0.044% NaH 2 PO 4 .H 2 O and 0.388% Na 2 HPO 4 .2H 2 O in water.

Lenses with a PAA-LbL base coat on top prepared in Example 3 are placed in a polypropylene lens packaging shell with 0.6 mL IPC salt solution (half of the saline solution is added before insertion of the lens). The blister is then sealed with metal foil and autoclaved for about 30 minutes at about 121 ° C. A crosslinked coating composed of three layers of PAA-x-PAE-x-poly (AAm-co-AA) is believed to be formed on the lenses during autoclaving.

The test lenses (packed / autoclaved in IPC saline solution, i.e. lenses with PAA-x-PAE-x-poly crosslinked coating (AAm-co-AA) above) do not exhibit debris adherence after being rubbed against a paper towel. The test lenses have a WBUT of more than 10 seconds. When viewed under a darkfield microscope, the cracking lines are visible after the test lenses are rubbed. The test lenses are much more lubricated than the 123 ΡΕ2461767 test lenses of Example 4 but not yet as lubricated as the control lenses packaged in PBS.

Example 6

An IPC salt solution is prepared by dissolving 0.02% poly (AAm-co-AA) (80/20) and 0.2% PAE (Kymene from Ashland as aqueous solution and used as received, azetidin content of 0 , Assayed with NMR) in PBS and adjusting the pH to 7.2-7.4. Then, the saline solution is treated by heating to and at about 70 ° C for 4 hours (thermal pre-drying). During this heat pretreatment poly (AAm-co-AA) and PAE are partially cross-linked (ie not consuming the azetidinium groups of PAE) to form a water-soluble thermally cross-linkable hydrophilic polymeric material containing azetidinium groups with the branched polymer network in the IPC saline solution. After the heat pretreatment the final salt solution IPC is filtered using a 0.22 micron polyether sulfone (PES) membrane filter and is cooled again to room temperature.

The PAA-LbL base coat lenses prepared in Example 3 are placed in a polypropylene lens packaging shell with 0.6 mL of the IPC saline solution (half of the saline solution is added before insertion of the lens) . The blister is then sealed with metal foil and autoclaved for about 30 minutes at about 121 ° C, forming a crosslinked coating (PAA-124 ΡΕ2461767 x-hydrophilic polymeric material) on the lenses.

Test lenses (packaged in heat-primed IPC saline, i.e. lenses coated with PAA-x-hydrophilic polymeric material on top) do not exhibit adherence of debris after being rubbed against a paper towel while the lenses (packed in PBS, i.e., lenses having a non-covalently bonded PAA layer on top) exhibit a severe adherence of debris. The test lenses have a WBUT of more than 10 seconds. When observed under a darkfield microscope, no cracking lines are visible after the test lenses are rubbed. Test lenses are much more lubricated in a finger rub test and are equivalent to control lenses. A number of experiments are performed to study the effects of the conditions (duration and / or temperature) of the heat pretreatment of the IPC salt solution on the surface properties of the resulting lenses coated with the IPC salt solution. Heat treatment times of about 6 hours or more at about 70øC result in lenses that are susceptible to adherence of debris similar to that of control lenses. It is believed that a longer preheating treatment may consume most of the azetidinium groups and as such the numbers of remaining azetidinium groups in the branched polymer network of the resulting water soluble polymer material are 125 ΡΕ2461767 insufficient to bind the material polymer to the PAA coating. Heat treatment for only 4 hours at 50 ° C results in lenses showing lines of surface cracking under dark field microscopy after being rubbed between the fingers similar to the test lenses in Example 5 where the IPC saline solution is not pre- heat treated. It is believed that a shorter preheating treatment can consume a small amount of azetidinium groups and as such the numbers of azetidinium groups remaining in the branched polymer network of the resulting water soluble polymer material are raised so that the resulting coating (PAA-x-hydrophilic polymeric material) on the lenses may have a too high cross-link density.

Example 7

Poly (acrylamido-co-acrylic acid) partial sodium salt (-90% solid, Poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from Polisciences, Inc. and used as received .

An IPC salt solution is prepared by dissolving 0.07% PAAm-PAA (90/10) and 0.2% PAE (Kymene from Ashland as aqueous solution and used as received, 0.46 azetidinium-assayed by NMR ) in PBS and adjusting the pH to 7.2-7.4. Then, the saline solution is pretreated thermally for about 4 hours at about 70 ° C (pre-heat treatment). During this thermal pretreatment, the poly (AAm-co-AA) and the PAE are partially cross-linked to each other (i.e., not consuming all the azetidinium groups of the PAE) to form a soluble, thermally cross-linkable hydrophilic polymeric material in water containing azetidinium groups within the branched polymer network in the IPC salt solution. After heat pretreatment, the IPC salt solution is filtered using a 0.22 micron polyether sulfone [PES] membrane filter and cooled back to room temperature.

The lenses with a PAA-LbL base coat prepared above in Example 3 are Lotrafilcon B (CIBA VISION CORPORATION) lenses which are dipped in acidic PAA propanol (ca. 0.1%, pH-2 , 5) and are placed in polypropylene shells for lens packaging with 0.6 ml of the pre-heat-treated IPC saline solution (half of the IPC saline solution is added before insertion of the lens). The blister is then sealed with metal foil and autoclaved for about 30 minutes at about 121 ° C, forming a crosslinked coating (PAA-x-hydrophilic polymeric material) on the lenses.

The test lenses (both Lotrafilcon B and the lenses of Example 3 having a PAA-x-hydrophilic polymer on top) exhibit no adherence of debris after being rubbed against a paper towel. The test lenses have a WBUT of more than 10 seconds. When viewed under a darkfield microscope, the cracking lines are visible after the test lenses are rubbed between the fingers. The lenses are extremely lubricated in qualitative tests of friction between the fingers.

Example 8

In the Experiments of Experiments (DOE), IPC salt solutions are produced to contain from about 0.05% to about 0.09% PAAm-PAA and from about 0.075% to about 0.19% PAE ( Kymene from Ashland, as an aqueous solution and used as received, 0.46 azetidinium-assayed with NMR) in PBS. The IPC salt solutions are thermally treated for 8 hours at 60øC and the lenses of Example 3 are packed in the pre-heat-treated IPC salt solutions. No differences in surface properties of the finished lens were observed and all lenses showed excellent lubrication, resistance to adhesion of debris, excellent wetting and no evidence of surface cracking.

Example 9

In the Experiments of Experiments (DOE), IPC salt solutions are produced to contain between about 0.07% PAAm-PAA and PAE sufficient to produce an initial azetidin content of approximately 8.8 millimoles / liter (-0 , 15% PAE). The pre-heat conditions are varied in a central composite project from 50øC to 70øC and the pre-reaction time is varied from about 4 to about 12 hours. A time of 128 ΡΕ2461767 24 hour pretreatment at 60øC is also tested. 10 ppm of hydrogen peroxide are then added to the saline solutions to prevent bioburden development and the IPC salt solutions are filtered using a 0.22 micron polyether sulfone [PES] membrane filter.

The lenses of Example 3 are packed in the pre-heat treated IPC salt solutions and the blisters are then autoclaved for 45 minutes at 121 ° C. All lenses have excellent lubrication, wetting and resistance to surface cracking. Some of the lenses exhibit paper towel debris adherence, as indicated in Table 1.

Table 1

Evaluation of the Adherence of Detrusts Temperature (° C) Time (h) 50 55 60 65 70 4 pass 6 pass pass 8 pass pass pass 10 pass pass 12 pass pass 24 failure 129 ΡΕ2461767

Example 10

Copolymers of methacryloxyethylphosphorylcholine (MPC) with a carboxyl-containing vinyl monomer (methacrylic acid (MA) of CH 2 = CH (CH 3) C (O) OC 2 H 4 OC (O) C 2 H 4 COOH (MS)) in the absence or presence of butyl methacrylate (BMA) are evaluated in a packaging interior coating system in combination with PAE. PBS containing NaCl (0.75% by weight), NaH 2 PO 4 is prepared. H20 (0.0536 wt%), Na2HP04.2H20 (0.3576 wt%) and water D1 (97.59 wt%) and 0.2% of PAE (polycup 3160) is added. The pH is adjusted to about 7.3. 0.25% of one of the various copolymers of MPC is then added to form an IPC salt solution and the IPC salt solution is thermally pretreated at 70 ° C for 4 hours (pre-heat treatment). During this heat pretreatment, MPC and PAE are partially cross-linked to each other (i.e., not consuming all the azetidinium groups of the PAE) to form a water-soluble, thermally cross-linkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC saline solution. After 4 hours the thermally pretreated IPC salt solution is filtered through 0.2 micron polyether sulfone [PES] membrane filters (Fisher Scientific catalog # 09-741-04, Thermo Scientific nalgene # 568-0020 ( 250 ml) 130 ΡΕ2461767

The lenses having a PAA-LbL base coat prepared in Example 3 above are packed in the pre-heat-treated IPC saline and autoclaved for about 30 minutes at 121øC. Table 2 shows that all lenses have excellent surface properties.

Table 2

MPC Copolymer * D.A. Fissures Lubrication Wetting WBUT (sec.) Poly (MPC / MA) 90/10 passes excellent excellent passes Poly (MPC / BMA / MA) 40/40/20 passes excellent excellent passes

Table 2 (Cont.)

MPC Copolymer * DA Fissures Lubrication WBUT (sec) Poly (MPC / BMA / MA) 70/20/10 passes excellent excellent passes Poly (MPC / BMA / MS) 70/20/10 passes excellent excellent passes * The numbers are mole percentages of monomer units in the copolymer. D.A. = Adherence of Debris. WBUT greater than 10 seconds.

Example 11

Lenses coated with PAA. The cast molded lenses from a lens formulation prepared in Example 3 according to the molding process described in Example 3 are extracted and dip coated in the following series of baths: MEK baths (22, 78 and 224 ΡΕ2461767 seconds); water bath Dl (56 seconds); 2 baths of PAA coating solution (prepared by dissolving 3.6g PAA (M.W., 450kDa, from Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds, separately; and 3 Dl water baths, each for 56 seconds.

Lenses coated with ΡΑΕ / ΡΆΆ. The above prepared lenses having a PAA-based coating are successively dipped into the following baths: PAE coating solution baths, which is prepared by dissolving 0.25% by weight PAE (Polycup 172 from Hercules) in water D1 and adjusting the pH to about 5.0 using sodium hydroxide and finally filtering the resulting solution using a 5 pm filter for 44 and 56 seconds, respectively; and 3 baths of Dl water each for 56 seconds. After this treatment, the lenses have a layer of PAA and a layer of PAE.

Lenses with PAA-x-PAE-x-CMC coatings on top. A batch of lenses having a PAA layer and a PAE layer on top are packed in a 0.2% sodium carboxymethylcellulose (CMC, Product # 7H 3SF PH, Aqualon of Ashland) in phosphate buffered saline (PBS) and the pH is then adjusted to 7.2-7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121Â ° C, forming crosslinked coatings (PAA-x-PAE-x-CMC) on the lenses. 132 ΡΕ2461767

Lenses with PAA-x-PAE-x-HA coatings on top. Another batch of lenses having a PAA layer and a PAE layer on top are packed in 0.2% hyaluronic acid (HA, Product # 6915004, Novozymes) in phosphate buffered saline (PBS) and the pH is then adjusted to 7.2 - 7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121Â ° C, forming crosslinked coatings (PAA-x-PAE-x-HA) on the lenses.

The lenses resulting either with PAA-x-PAE-x-CMC coating or with PAA-x-PAE-x-HA coating on top do not exhibit Sudan Black patches, no debris adherence, and no cracks at microscopic observation . PAA-x-PAE-x-CMC coated lenses over the top have a mean contact angle of 30 ± 3 degrees, while PAA-x-PAE-x-HA coated lenses over the top have a contact angle average of 20 + 3 degrees.

Example 12

Preparation of the IPC solution. A reaction mixture is prepared by dissolving 2.86 wt% mPEG-SH 2000 (Methoxy-Poly (Ethylene glycol) -Tiol, Avg MW 2000, Product # MPEG-SH-2000, Laysan Bio Inc.) at the same time as 2 % by weight of PAE (Kymene from Ashland as an aqueous solution and used as received, 0.46 azetidinium-assayed with NMR) in PBS and the final pH adjusted to 7.5. The solution is heat treated for about 4 hours at 45øC (pre-heat treatment). During this thermal pretreatment, mPEG-SH 2000 and PAE are reacted with one another to form a thermally crosslinkable, water-soluble hydrophilic polymeric material containing azetidinium groups and chemically grafted polyethylene glycol polymer chains. After the heat treatment, the solution is diluted 10-fold with 0.25% sodium citrate containing PBS, pH adjusted to 7.2-7.4 and then filtered using polyether sulfone (PES) membrane filter, of 0.22 microns. The IPC salt solution contains 0.286 wt% of hydrophilic polymeric material (consisting of about 59 wt% of MPEG-SH-2000 chains and about 41 wt% of PAE chains) and 0.25 wt% sodium citrate hydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2 PO4 · H2 O and 0.353% Na2HPO4.2H2 O in water.

Lenses with crosslinked coatings on top. The PAA-coated lenses of Example 11 are packed in the above IPC saline solution in polypropylene liner packaging shells and are then autoclaved for about 30 minutes at about 121 ° C, forming a crosslinked coating on the lens.

The finished lenses exhibit no adherence of debris, no cracking lines after being rubbed. The lenses are heavily lubricated in a finger rub test comparable with the PAA coated control lenses.

A number of experiments are carried out to study the effects of the conditions (reaction time and concentration of the mPEG-SH2000 solution (with constant concentration of 2% PAE) on the surface properties of the resulting lenses coated with the IPC salt solution The results are shown in Table 3.

Table 3 1. Concentration of PAE: 2% by weight.

[mPEG-SH2 0 0 0] 1 (p%) Reaction Time @ 45 ° C (h) D.A. Cracking Lubrication WCA Test 1 Test 2 2.86 0 0.2 0.2; 2, NA 3 3 17 2.86 0.5 0.0 0.2; 0.2 2-3 2 21

(MPEG-SH2 0 0) 1 (wt%) Reaction Time @ 45Â ° C (h) D.A. Cracking WCA Lubrication Test 1 Test 2 2.86 2 0.00; 0.0 2 2 20 2.86 4 0.0 0.0; 0.0 1-2 1 370, 540 0.2; NA 4 3-4 15 1.5 40 0.0; NA 3 3 20 6 4 0 0.0; NA 0-1 0 51 D.A. = adherence of debris; WCA = angle of contact with water. As the concentration of the mPEGSH2000 solution increases, the lubrication of the lens increases by 135 ΡΕ2461767 compliance. It is believed that the increase in the contact angle of the surface may be due to the increasing density of terminal methyl groups on the surface with increasing grafting density. At high grafting densities, corresponding to a solution concentration of 0.6%, the contact angle approximates the measurements obtained on the flat substrates grafted on the polyethylene glycol (PEG) monolayer (Reference: Langmuir 2008, 24, 10646-10653 ).

Example 13 A series of experiments is performed to study the effects of the molecular weight of mPEG-SH. The IPC salt solution is prepared in a similar manner to the process described in Example 12. However, the following mPEG-SH are used to prepare the saline: mPEG-SHIOOO, mPEG-SH2000, mPEG-SH5000 and mPEG-SH20000. All saline solutions are heat-treated at 45øC for 4 hours and 10-fold dilution. The results and reaction conditions are given below: mPEG -SH D. A. Cracking Lubrication WCA M.W. (Daltons) Cone. (%) * Test 1 Test 2 1000 1.5 No No 2 1 21 1000 2, 86 No No 1 1 27 2000 1.5 No No 2 2 28 2000 2.86 No No \ -1 1 O 0 21 136 ΡΕ2461767 5000 1.5 No No 2 2 18 5000 2.86 No No 0-1 0-1 26 20000 1.5 No No 3 2 21 20000 2.86 No No 2 1 21 DA = adherence of debris; WCA = contact angle with water. * Initial concentration of MPEG-SH in IPC saline containing 2% of PAE before heat pretreatment and 10-fold dilution.

Example 14 A reaction mixture is prepared by dissolving 2.5% mPEG-SH 2000, 10% PAE (Kymene from Ashland as an aqueous solution and used as received, 0.46 azetidinium-assayed NMR) in PBS and 0.25% sodium citrate dihydrate. The pH of this solution is then adjusted to 7.5 and also degassed by bubbling nitrogen gas through the vessel for 2 hours. This solution is subsequently thermally treated for about 6 hours at 45 ° C forming a thermally crosslinkable hydrophilic polymeric material containing mPEG-SH-2000 groups chemically grafted onto the polymer by reaction with the azetidinium groups in PAE. After the heat treatment, the solution is diluted 10-fold using PBS containing 0.25% sodium citrate, pH adjusted to 7.2-7.4 and then filtered using a polyether sulfone membrane filter (PES ) of 0.22 microns. The final salt solution IPC contains about 0.30% by weight of the polymeric material (consisting of about 17% by weight of mPEG-SH-2000 and 137 ΡΕ2461767 about 83% by weight of PAE) and 0.25% of sodium citrate dihydrate.

The PAA coated lenses of Example 11 are packed in the above IPC saline solution in polypropylene liner packaging shells and then autoclaved for about 30 minutes at about 121 ° C, forming a crosslinked coating on the lenses.

The finished lenses have no debris adherence, no cracking lines after being rubbed. Test lenses are highly lubricated in a digital friction test comparable to PAA coated control lenses.

Example 15 A reaction mixture is prepared by dissolving 3.62% mPEG-NH2 550 (methoxy poly (ethylene glycol) amine, MW-550 (Product # MPEG-NH2-550, Laysan Bio Inc) at the same time as 2% PAE (Kymene from Ashland as an aqueous solution and used as received, 0.46 azetidinium ratio assayed with NMR) in PBS and the final pH is adjusted to 10. The solution is heat-treated for about 4 hours at 45 ° C forming a thermally crosslinkable hydrophilic polymeric material containing MPEG-NH2 -550 groups chemically grafted onto the polymer by reaction with the azetidinium groups in PAE After the heat treatment, the solution is diluted with 10-fold PBS containing 0.25% 138 ΡΕ2461767 sodium citrate, pH adjusted to 7.2-7.4 and then filtered using a 0.22 micron polyether sulfone (PES) membrane filter.The final IPC salt solution contains about 0.562% by weight of polymeric material (consisting of 64% by weight of MPEG-SH-20 00 and about 36% by weight of the PAE) and 0.25% of sodium citrate dihydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2 PO4 · H2 O and 0.353% Na2HPO4.2H2 O in water.

The PAA coated lenses of Example 11 are packed in the above IPC saline solution in polypropylene liner packaging shells and then autoclaved for about 30 minutes at about 121 ° C, forming a crosslinked coating on the lenses.

The finished lenses exhibit no debris adherence and no cracking lines were observed after rubbing the lenses digitally (between the fingers).

Example 16

Poloxamer 108 (sample) and nelfilcon A (CIBA VISION) are used as received. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by the modification of a polyvinyl alcohol (for example, Gohsenol KL-03 from Nippon Gohsei or the like) with N- (2,2-Dimethoxyethyl) acrylamide under cyclic acetal formation reaction conditions (Buhker et al., CHIMIA, 53 (1999), 269-274, here incorporated by reference in its entirety). About 2.5% vinyl alcohol units in nelfilcon A are modified by N- (2,2-Dimethoxyethyl) acrylamide. The IPC salt solution is prepared by dissolving 0.004% poloxamer 108, 0.8% nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl and 1.1% disodium hydrogen phosphate (dihydrate) in water D1. The saline solution is thermally pre-treated by stirring for 2 hours at about 65-70 ° C. After the heat pretreatment, the saline solution is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.

The lenses prepared in Example 3 are placed in a polypropylene lens packaging shell with 0.6 mL IPC salt solution (half of the saline is added before lens insertion). The blister is then sealed with metal foil and autoclaved for about 30 minutes at 121 ° C.

The test lenses do not exhibit debris adherence after being rubbed against a paper towel. The lenses had a WBUT greater than 10 seconds. When observed under a dark-coated microscope, no cracking lines are visible after rubbing the lenses between the fingers. The lens is much more lubricated than the lenses of Example 4 but not yet as lubricated as the PAA coated control lenses 140 ΡΕ2461767 packaged in PBS.

Example 17 A. Synthesis of 80% of polysiloxane extended by ethylenically functionalized chain

Polymethylsiloxane KF-6001A (α, β-bis (2-hydroxy-toxopropyl) -polydimethylsiloxane, Mn = 2000, Shin-Etsu) and KF-6002A (α, ω-bis (2-hydroxyethoxypropyl) polydimethylsiloxane, Mn = 3400 from Shin-Etsu) are separately dried at about 60øC for 12 hours (or overnight) under high vacuum in a single colored flask. The OH-equivalent molar weights of KF-6001A and KF-6002A are determined by titration of hydroxyl groups and are used to calculate the millimolar equivalent to be used in the synthesis.

A 1 liter reaction vessel is evacuated overnight to remove moisture and the vacuum is quenched with dry nitrogen. 75.00 g (75 meq) dry KF6001A is charged into the reactor and then 16.68 g (150 meq) freshly distilled IPDI is added to the reactor. The reactor is purged with nitrogen and heated to 45øC with stirring and then 0.30 g of DBTDL is added. The reactor is sealed, and a positive flow of nitrogen is maintained. Exotherm occurs, whereupon the reaction mixture is allowed to cool and is stirred at 55 ° C for 2 hours. After reaching the exotherm, 248.00 g (150 meq) of dry KF6002A is added to the reactor at 55 ° C and then 100 μl of DBTDL is added. The reactor is stirred for four hours. Heating is discontinued and the reactor is allowed to cool overnight. The nitrogen bubble is discontinued and the reactor is opened to the atmosphere for 30 minutes with moderate agitation. A hydroxyl-terminated chain-extended polysiloxane having 3 segments of polysiloxane, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) is formed.

For 80% of ethylenically functionalized polysiloxane, 18.64 g (120 meq) of EMI is added to the reactor at the same time as 100 μΐ of DBTDL. The reactor is stirred for 24 hours and then the product (80% EC-PDMS capped by IEM) is decanted and stored under refrigeration. B. Synthesis of non-UV absorptive amphiphilic branched polysiloxane prepolymer.

A 1-L jacketed reactor is equipped with a 500-mL addition funnel, head stirring, reflux condenser with nitrogen / vacuum inlet valve adapter, thermometer, and sampling adapter. The reactor is charged with 45.6 g of 80% of the above-prepared IEM-capped CE-PDMS and is sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, 27.80 g of tris (trimethylsilyl) siloxopropyl methacrylate (TRIS) in 279 g of ethyl acetate is loaded into the addition funnel. The reactor is degassed at &lt; 1 mbar for 30 minutes at RT with a high vacuum pump. The monomer solution is degassed at 100 mbar and RT for 10 minutes 142 ΡΕ2461767 for three cycles, quenching the vacuum with nitrogen between the degassing cycles. The monomer solution is then charged into the reactor and then the reaction mixture is stirred and heated to 67 ° C. While heated, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) and 0.26 g of azoisobutyronitrile dissolved in 39 g of ethyl acetate is charged into the addition funnel and deoxygenated three times at 100 mbar , RT for 10 minutes. When the reactor temperature reaches 67øC, the initiator / CTA solution is added to the PDMS / monomer solution in the reactor. The reaction is allowed to proceed for 8 hours and then heating is discontinued and the reactor temperature is brought to room temperature within 15 minutes. The resulting reaction mixture is then siphoned to a dry single-necked flask with airtight cap and 4.452 g of EMI is added with 0.21 g of DBTDL. The mixture is stirred 24 h at room temperature forming non-UV absorptive amphiphilic branched polysiloxane prepolymer. To this mixture in solution is added 100 æl of hydroxy tetramethylene piperonyloxy solution in ethyl acetate (2 g / 20 mL). The solution is then concentrated to 200 g (-50%) using rotary evaporator at 30øC and is filtered through filter paper having a pore size of 1 æm. After solvent exchange for 1-propanol, the solution is further concentrated to the desired concentration. C. Synthesis of UV absorptive amphiphilic branched polysiloxane 143 ΡΕ2461767 Prepolymer.

A 1-L jacketed reactor is equipped with a 500-mL addition funnel, head stirring, reflux condenser with nitrogen / vacuum inlet valve adapter, thermometer, and sampling adapter. The reactor is then charged with 45.98 g of 80% of the above-prepared IEM-capped CE-PDMS and is sealed. A solution of 0.512 g of (HEMA), 25.354 g of DMA, 1.38 g of Norbloc methacrylate, 2634 g of TRIS, in 263 g of ethyl acetate is charged into the addition funnel. The reactor is degassed at &lt; 1 mbar for 30 minutes at RT with a high vacuum pump. The monomer solution is degassed at 100 mbar and RT for 10 minutes over three cycles, quenching the vacuum with nitrogen between the degassing cycles. The monomer solution is then charged into the reactor and then the reaction mixture is stirred and heated to 67 ° C. While heated, a solution of 1,480 g of mercaptoethanol (chain transfer agent, CTA) and 0.260 g of azobalbutyronitrile dissolved in 38 g of ethyl acetate is charged into the addition funnel and deoxygenated three times at 100 mbar, at room temperature for 10 minutes. When the reactor temperature reaches 67øC, the initiator / CTA solution is added to the PDMS / monomer solution in the reactor. The reaction is allowed to proceed for 8 hours and then heating is discontinued and the reactor temperature is brought to room temperature within 15 minutes. 144 ΡΕ2461767 The resulting reaction mixture is then siphoned to a dry single-necked flask with an air-tight cap and 3.81 g of ethyl isocyanate acrylate are added with 0.15 g of DBTDL. The mixture is stirred 24 h at room temperature forming a UV absorbing amphiphilic branched polysiloxane prepolymer. To this mixture in solution are added 100 μl of hydroxy tetramethylene piperonyloxy solution in ethyl acetate (2 g / 20 ml). The solution is then concentrated to 200 g (-50%) using rotary evaporator at 30øC and is filtered through filter paper having a pore size of 1 æm.

D-1: Lens formulation with non-UV absorptive polysiloxane prepolymer

In a 100 ml amber flask is added 4.31 g of the solution of the synthesized macromer (82.39% in 1-propanol) prepared above. In a 20 mL vial, 0.081 g of TPO and 0.045 g of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are dissolved in 10 g of 1-propanol and then transferred to the macromer solution . After the mixture is concentrated to 5.64 g using rotary evaporator at 30øC, 0.36 g of DMA is added and the formulation is homogenized at room temperature. 6 g of clear lens formulation is obtained. D-2: Lens Formulation with UV Absorbing Polysiloxane Prepolymer (4% DMA) 145 ΡΕ2461767

In a 100 mL amber flask is added 24.250 g of macromer solution prepared above (43.92% in ethyl acetate). In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent are removed using rotary evaporator at 30øC, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. To this mixture 0.6 g of DMA is added and the formulation is homogenized at room temperature. 15 g of D-2 is obtained for clear lens. D-3: Lens formulation with UV absorbent polysiloxane prepolymer (2% DMA / 2% HEA)

In a 100 mL amber flask is added 24.250 g of macromer solution prepared above (43.92% in ethyl acetate). In a 50 mL vial, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent are removed using rotary evaporator at 30øC, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. 0.3 g of DMA and 0.3 g of HEA are added to this mixture and the formulation is homogenized at room temperature. 15 g of D-3 is obtained for clear lens. 146 ΡΕ2461767

Example 18

Example E: Covalent attachment of coating polymers to modified PAE

Monomers containing amine groups, N- (3-Aminopropyl) methacrylamide hydrochloride (APMAA-HCl) or N- (2-aminoethyl) methacrylamide hydrochloride (AEMAA-HCl) are purchased from Polysciences and used as received. Poly (amidoamine epichlorohydrin) (PAE) is received from Ashland as an aqueous solution and is used as received. Poly (acrylamido-co-acrylic acid) (poly (AAm-co-AA) (90/10) from Polysciences, Laysan Bio mPEG-SH and poly (MPC-co-AeMA) (i.e., a copolymer of methacryloyloxyethylphosphorylcholine ( The APMAA-HCl monomer is dissolved in methanol and added to the lens formulations D1, D-2 and D-3 (prepared in Example 17) to achieve a concentration of 1% by weight The reactive salt solution for packaging is prepared by dissolving the components indicated in Table 4 at the same time as appropriate buffer salts in water D. The salt solution is heat-pretreated by stirring for 8 hours at about 60 C. After the heat pretreatment, the saline solution is allowed to cool to room temperature and then filtered using a PES filter of 0.2 μιη ΡΕ 2461767 147.

Table 4

Sample of saline for packaging 1 2 3 4 5 pH 7.4 7.4 7.4 8 8 PAE 0.2% 0.2% 0.2% 0.2% 0.2% Poly (AAm-co- AA) (90/10) 0.07% 0.2% - - - mPEG-SH, Mw = 2 0 0 0 - 0.3% - - mPEG-SH, Mw = 10 0 0 0 _ _ _ 0 , 2% Poly (MPC-Co-AeMA) (90/10) - - - - 0.2% The Dl formulation prepared in Example 17 is modified by the addition of the APMAA-HCl monomer (APMMA- 1: 1 methanol: propanol) and cured at 16 mW / cm 2 with 330 nm filter. Formulations D-2 and D-3 prepared in Example 17 are modified by addition of the APMNAA-HCl monomer and cured at 4.6 mW / cm 2 with a 380 nm filter.

DSM lenses. Female portions of polypropylene lens molds are filled with about 75 microliters of a lens formulation prepared as above and the molds are closed with the male portion of the lens polypropylene molds (curved base molds). Contact lenses are obtained by curing the molds closed for about 5 minutes with a source of irradiation (Hamamatsu lamp with filter cut from 330 nm to a 148 ΡΕ2461767 intensity of about 16 mW / cm2.

LS Lenses. LS lenses are prepared by cast molding from a lens formulation prepared as above in a reusable mold, similar to the mold shown in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6). The mold comprises a female mold half made of CaF2 and a male mold half made of PMMA. The UV irradiation source is a Hamamatsu lamp having a cut filter of 330 nm at an intensity of about 4.6 mW / cm 2. The lens formulation in the template is irradiated with UV irradiation for about 30 seconds. The APMAA-HCl modified formulation D-1 is cured according to the DSM and LS methods described above, while the D-2 or D-3 lens formulation is cured according to the LS method described above.

The molded lenses are extracted into methylethyl ketone, hydrated and packed into one of the saline solutions described in Table 4. The lenses are placed in a polypropylene liner packaging shell with 0.6 mL of IPC saline (half of the saline solution is added before inserting the lens). The blister is then sealed with metal foil and autoclaved for 30 minutes at 121 ° C. The evaluation of the lens surface shows that 149 ΡΕ2461767 all test lenses had no debris after they had been rubbed against a paper towel. When observed under a dark field microscope, no cracking lines were visible after rubbing the lenses between the fingers. Lens surface wetting (WBUT), lubrication and contact angle are measured and the results are abbreviated in Table 5. Lenses are made according to the DSM method unless otherwise specified. Lubrication is rated on a qualitative scale from 0 to 5 where the lower numbers indicate higher lubrication. In general, all properties shown improve after the coating is applied to the inside of the package.

Table 5

Formulation for the manufacture of lenses Salt solution1 WBUT (seconds) Lubrication Contact angle [fi] Dl as control 1 0 4-5 114 (APMAA-free) 3 0 4 119 1 10 0-1 104 Dl w / 1% APMAA 3 2 0-1 99 1 0 4-5 115 D 2 as contrlo 3 0 3 107 (APMAA-free) 4 o 2 3-42 1162 1 5 2-3 90 D 2 w / 1% APMAA 3 6 1 95 150 ΡΕ 2461767

2. LS Lenses 4 5-102 32 1062 D3 w / 1% APMAA 2 9 3-4 103 3 14 2-3 91 4 15 3 54 5 13 2 69 1. The number is the number of the saline solution presented in Table 4.

Example 19

Preparation of Formulations for Lenses. A lens formulation is prepared by dissolving the components in 1-propanol to have the following composition: about 32% by weight of the EC-PDMS macromer prepared in Example 2, about 21% by weight TRIS-Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of visitint (5% TRIS dispersion of phthalocyanine blue pigment of copper), about 0.8% by weight DMPC, about 200 ppm H-time, and about 22% by weight of 1-propanol.

Lens Preparation. The lenses are prepared by casting from the above prepared lens formulation into a reusable mold (quartz female half and male half glass mold), similar to the mold shown in Figs. 1-6 of U.S. patent applications 7,384,590 and 7,387,759 (Figs 1-6). The 151 ΡΕ2461767 lens formulation in the molds is irradiated with UV irradiation (13.0 mW / cm 2) for about 24 seconds. PAA coating solution. A PAA coating solution is prepared by dissolving an amount of PAA (MW: 450kDa, from Lubrizol) in a given volume of 1-propanol to have a concentration of about 0.36% by weight and the pH is adjusted with formic acid to about 2.0.

Lenses coated with PAA. The cast molded contact lenses as above are drawn and dip coated from the following series of baths: D1 water bath (about 56 seconds); 6 baths of MEK (about 44, 56, 56, 56, 56, and 56 seconds, respectively; weight, acidified with formic acid to about pH 2.0) in 100% 1-propanol (ca. 44 seconds); a 50% / 50% water / 1-propanol bath (ca. 56 seconds) , 4 DI water baths for about 56 seconds, a PBS bath for about 56 seconds, and a DI water bath for about 56 seconds.

IPC saline solution. Partial sodium salt of poly (AAm-co-AA) (-90% solids, poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from Polysciences, Inc. and used as received. PAE (Kymene, an 0.46 azetidinium assayed with NMR) is purchased from Ashland as an aqueous solution and is used as received. An IPC salt solution is prepared by dissolving about 0.07% w / w poly (AAm-co-152 ΡΕ2461767 ΑΑ) (90/10) and about 0.15% PAE (a millimolar equivalent of the initial azetidinium of about of 8.8 millimoles) in PBS (about 0.044% w / w NaH 2 PO 4 .H 2 O, about 0.388% w / w Na 2 HPO 4 .2H 2 O, about 0.79% w / w NaCl), and the pH to 7.2-7.4. Then, the IPC salt solution is pretreated thermally for about 4 hours at about 70 ° C (pre-heat treatment). During this heat pretreatment, poly (AAm-co-AA) and PAE are partially cross-linked to each other (i.e., not consuming all azetidinium groups of PAE) to form a water-soluble thermally cross-linkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC salt solution. After the heat pretreatment, the IPC salt solution is filtered using a 0.22 micron PES polyether sulfone membrane filter and is cooled back to room temperature. Then, 10 ppm of hydrogen peroxide is added to the final IPC saline to prevent the development of bioburden and the IPC saline solution is filtered using a 0.22 micron PES membrane filter.

Application of vim reticulated coating. Lenses having a PAA-LbL base coat back prepared above are placed in polypropylene lens packaging shells (a lens shell) with 0.6 mL of the IPC saline solution (half of the saline solution is added before inserting the lens ). The blisters are then sealed with metal foil and autoclaved for about 30 minutes at about 121øC, forming SiH3 153 ΡΕ2461767 contact lenses with crosslinked coatings (PAA-x-hydrophilic polymeric material).

Characterization of SiHy lenses. The resulting SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymeric material) do not exhibit adhesion of debris after they have been rubbed against a paper towel while the control lenses (packed in PBS, i.e., lenses with a layer of non-covalently bonded PAA) exhibit severe adherence of debris. The lenses have an oxygen permeability (Dkc or Dk intrinsic calculated) of 146 barrers, a mass modulus of 0.76 MPa, a water content of about 32% by weight, a relative ionic permeability of about 6 relative to Alsacon lenses), a contact angle of from about 34 to 47 degrees, a WBUT of more than 10 seconds. When observed under a darkfield microscope, no cracking lines are visible after rubbing the test lens. The lenses are heavily lubricated in a friction test between the fingers and equivalent to the control lenses.

Example 20

The SiHy lenses and the IPC salt solutions in lens packs after autoclaving, which are prepared in Examples 6, 14 and 19, are subjected to the following biocompatibility studies. 154 ΡΕ2461767

In-vitro evaluation of cytotoxicity. SiHy lenses are evaluated by the USP Direct Contact Material Test. Lens extracts are evaluated by the USP MEM Elution Assay and the CEN Cell Development Inhibition of the ISO and the IPC saline in the packages after autoclaving is evaluated by a Modified Elution Assay. All lenses and lens extracts evaluated are well within the acceptance criteria for each test and no unacceptable cytotoxicity is observed.

In-vivo testing. Systemic Rat Toxicity of ISO shows that there is no evidence of systemic toxicity in the rat with lens extracts. The ISO Rabbit Eye Irritation Study shows that IPC saline in the packages after autoclaving is not considered to be an irritant to rabbit eye tissue. Disposable lenses used daily for 22 consecutive days are non-irritating in the rabbit model and the eyes treated with the test lenses are similar to those treated with the control lenses. The Study of

Sensitization of ISO (Packaging Solutions Maximization Tests in Guinea pig) shows that IPC saline after autoclaving does not cause any sensitization of delayed dermal contact in the guinea pig. The ISO Sensitization Study (Cobalt Lens Extraction Maximization Tests) shows that the sodium chloride extracts and the sesame oil from the lenses do not cause sensitization of delayed dermal contact in the guinea pig. 155 ΡΕ2461767

Genotoxicity tests. When the IPC salt solutions of the lens packs and the SiHy lens extracts are tested on a Reverse Bacterial Mutation Assay (Ames Test), it is discovered that the lens extracts and the IPC salt solutions are considered to be non-mutagenic to the strains Salmonella typhimurium TA98, TA100, TA1535 and TA1537 and Escherichia coli WPuvrA. When the SiHy lens extracts are tested in a Mammalian Erythrocyte Micronucleus Assay, they have no clastogenic activity and are negative in the mouse medullary micronucleus test. When saline solutions from lens packages are tested according to the Chinese Hamster Ovary Chromosome Aberration Test, IPC salt solutions are negative for the induction of structural and numerical chromosome aberrations using CHO cells in both activated and non-activated test systems activated by S9. When the SiHy lens extracts are tested according to the Cell Gene Mutation Test (Rat Lymphoma Mutagenesis Assay), the lens extracts are indicated to be negative in the Rat Lymphoma Mutagenesis Assay.

Example 21

The surface compositions of the preformed SiHy contact lenses (i.e., SiHy contact lenses without any coating and before the PAA base coat is applied), the PAA coating lenses (i.e., those lenses before being sealed and autoclaved in lenses packs with IPC saline), and the SiHy contact lenses with a cross-linked coating, all of which are prepared according to the procedures described in Example 19, are determined by characterizing dry contact lenses with X-ray photoelectron spectroscopy (XPS). XPS is a method for measuring the surface composition of the lenses having a sampling depth of about 10 nm. The surface compositions of the three types of lenses are listed in Table 6.

Table 6

Surface Atomic Composition (%) Lens SiHy C N 0 F * Si Preformed (uncoated) 58.0 6.2 23.0 oo 12.1 With PAA coating &gt; 1.6 42.1 2.9 With crosslinked coating 59.1 10.8 25.4 4-1: 1 Fluoride is detected, most likely from surface contamination during the XPS analysis of the process vacuum drying Table 6 shows that when a PAA coating is applied over a SiHy (preformed, uncoated) lens, the silicon atomic composition is substantially reduced (from 12.1% to 4.5%) and the atomic nitrogen composition is also reduced (from 6.2% 157 ΡΕ2461767 to 1.6%). When a crosslinked coating is most applied over a PAA coating, the surface composition is predominantly carbon, nitrogen and oxygen, all of which constitute the atomic composition (excluding hydrogen because XPS does not have hydrogen in the surface composition). These results indicate that the outermost layer of the crosslinked coating SiHy contact lens is likely to consist essentially of hydrophilic polymeric material which is the reaction product of poly (AAm-co-AA) (90/10) (60% C, 22% O and 18% N) and PAE.

The following commercial lenses which are vacuum dried are also subjected to XPS analysis. The surface compositions of such commercial SiHi contact lenses are listed in Table 7.

Table 7

Surface Atomic Composition (%) CN 0 p * Si N & D® Aqua ™ 68, 4 9.1 18.6 1.5 2.4 Air Optix® Aqua ™ 67, 7 9.9 18.2 1.9 2 , 4 PureVision® 58.2 26.9 26.0 1.1 7.9 Award 61, 1 6.9 23.6 1.8 6.6 Acuvue® Advance® 61, 1 4, 9 24, 9 0 , 7 8.4 Acuvue® Oasys® 61.5 5 0.04 24.6 4 8.5 8.5 TruEye ™ 63.2 24.9 24.2 0.8 7.0 Biofinity® 46.5 1.4 28 , 9 5.3 17.9 158 ΡΕ2461767

Avaira ™ 52.4 2.5 27.8 8 4.2 13.1 *: Fluoride was also detected in Advance, Oasys and TruEye lenses, most likely of surface contamination during XPS analysis of the vacuum drying process

It has been discovered that a SiHy contact lens of the invention has a nominal silicon content of about 1.4% on the surface layer, much lower than commercially available SiHy commercial lenses (Acuvue® Advance®, Acuvue® Oasys ®, TruEye ™, Biofinity®, Avaira ™) and PureVision® (with plasma oxidation) and Prize ™ (with unknown plasma treatment) and even lower than lenses with a plasma deposited coating having a thickness of about 25 nm (N & D® Aqua ™ and Air Optix® Aqua ™). This greatly reduced value of Si% is comparable to the atomic percentage of silicon in a control sample, Goodfellow's polyethylene (LDPE, d = 0.015 mm, LS356526 SDS, ET 31111512, 3004622910). These results indicate that the very low value in the XPS analysis of the vacuum dried SiHy contact lens of the invention may be due to contaminants introduced during the preparation process including the vacuum drying process and XPS analysis, similar to the observed fluorine content on lenses that do not contain fluoride. Silicone has been successfully preserved in XPS analysis in the SiHy contact lenses of the invention.

XPS analysis of the SiHy contact lenses of the invention (prepared according to 159 ΡΕ2461767 processes described in Example 19), commercial SiHy contact lenses (CLARITI ™ 1 Day, ACUVUE® TruEye ™ (narafilcon A and narafilcon B) ), Goodfellow polyethylene sheets (LDPE, d = 0.015 mm, LS356526 SDS, ET 31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, i.e., non-silicone hydrogel lenses), ACUVUE® Moist in polyhydroxyethylmethacrylate hydrogel, i.e., non-silicone hydrogel lenses). All lenses are vacuum dried. Polyethylene sheets, DAILIES® and ACUVUE® Moist are used as controls because they do not contain silicon. The silicon atomic compositions in the surface layers of the test samples are as follows: 1.3 + 0.2 (polyethylene sheet); 1.7 + 0.9 (DAILIES®); 2.8 + 0.9 ACUVUE® Moist; 3.7 + 1.2 (three SiHy lenses prepared according to the procedures described in Example 19); 5.8 + 1.5 (CLARITI ™ 1 Day); 7.8 + 0.1 (ACUVUE® TruEye ™ (narafilcon A)); and 6.5 + 0.1 (ACUVUE® TruEye ™ (narafilcon B)). The results for the SiHy contact lenses of the invention are closer to traditional hydrogels than to silicone hydrogels.

Example 22 Fluorescein labeled PAA (PAA-F) PAA-F is synthesized at home by covalently attaching 5-aminofluorescein to PAA (Mw 450k). The degree of labeling of fluorescein is a small%, for example about 2 mole% (or n / (m + n) = 2% in the formula shown at 160 ΡΕ2461767 below), s'; (I.e.

Fluorescence labeled PAA (PAA-F) X: Fluorescein portion

Lens Preparation Leak-molded lenses are prepared from the above lens formulations prepared in Example 19 in a reusable mold (half quartz female mold and half glass male mold), similar to the mold shown in Figs. 1-6 of U.S. patent applications 7,384,590 and 7,387,759 (Figs 1-6). The lens formulation in the molds is irradiated with UV irradiation (13.0 mW / cm 2) for about 24 seconds.

PAA-F Coating Solution A PAA-F coating solution is prepared by dissolving an amount of PAA-F back prepared in a given volume of 1-PrOH / water (95/5) solvent mixture to have a concentration of about 0.36% by weight and the pH is adjusted with formic acid to about 2.0. About 5% of water is used to dissolve PAA-F. 161 ΡΕ2461767

Lenses coated with ΡΑΆ.

Leak molded lenses are drawn and dip coated in the following series of baths: Dl water bath (about 56 seconds); 6 MEK baths (about 44, 56, 56, 56, 56 and 56 seconds, respectively); Dl water bath (about 56 seconds); 1 bath of PAA-F coating solution (about 0.36% by weight, acidified with formic acid to about pH 2.0) in a solvent mixture of PrOH / water (95/5) (ca. 44 seconds) ; 1 bath of a 50% / 50% water / l-propanol bath (about 56 seconds); 4 baths of water Dl, each for about 56 seconds; a PBS bath for about 56 seconds; and 1 bath of water D1, for about 56 seconds.

Application of reticulated coating.

The above lenses prepared with a PAA-LbL coating on top are placed in polypropylene lens packaging shells (one lens per shell) with 0.6 ml of the IPC salt solution prepared according to the procedures described in Example 19 (half of the saline solution is added before inserting the lens). The blisters are then sealed with metal foil and autoclaved for about 30 minutes at about 121Â ° C, forming SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymeric material). 162 ΡΕ2461767

Confocal laser fluorescence microscopy.

A cut of a hydrated SiHy lens with crosslinked coating (back prepared) is cut and placed between two glass slides and the image is collected on a laser confocal fluorescence microscope (# Zeiss model LSM 510 Vis). It is swept from the curved front side of the lens to the curved side of the lens base, or vice versa. The presence of PAA-F is shown by green fluorescence and microscopic images of laser confocal fluorescence can be obtained. Examination of microscopic images of laser confocal fluorescence reveals that the PAA-F rich layer is present on both lens surfaces (anterior and posterior surfaces) and on the peripheral edge, while no FPA-F is observed in mass matter of the hydrated lens.

Fluorescence intensity profiles are examined by cutting the lens along a line passing through both the anterior and posterior normal surfaces to the posterior surface. Figure 3 shows two representative profiles of the fluorescence intensity along two lines through the lens cut, one at the point where the lens thickness is about 100 μm (panel A) and the other at the point where the thickness of the lens is about 200 μm (panel B). The original points in Figure 3 are the central points between the anterior and posterior surfaces along the lines. It can be seen in Figure 3 that there is a PAA-F rich layer near 163 ΡΕ2461767 of the outermost surfaces of the crosslinked SiHy lens, no PAA-F is present in the lens mass and the thickness of the coating is similar in these two cuts regardless of the thickness of the cuts. The thickness of the PAA-F rich layer (i.e. the sum of infusion depth in the hydrogel outer layer and the penetration depth of the PAA-F in the mass material (i.e., in the inner layer)), or the layer of (for the schematic illustration see Figure 2, transition layer 115), can be calculated from the fluorescence intensity profile shown in Figure 3. The possible transition layer thickness (PAA-F rich layer) is calculated by distance from zero intensity, after crossing the peak intensity, to zero intensity again. Since there is a possible contribution of unknown factors (such as dispersion) to the fluorescence intensity, the minimum thickness of the layer is the thickness for which a fluorescent intensity of at least 10% of maximum peak intensity is retained. Based on this calculation, the minimum thickness of the PAA-F rich layer could be at least about 5 microns. It should be noted that the thickness for PAA-coated SiHy lenses of the foregoing Examples could be higher considering that the concentration used is 10-fold higher than the concentration of PAA-F used in these experiments. A lens with a thicker coating may also be prepared using a coating time 164 ΡΕ2461767 per dive greater than 44 seconds, with 44 seconds being the dip coating time for the PAA-F used in this experiment. A thicker coated lens may also be prepared using PAA of different molecular weight.

Example 23

This example illustrates how to determine the water content of the crosslinked coating (the two outer layers in hydrogel) in a SiHy of the invention). In an effort to determine the potential water content of the crosslinked coating of the SiHi lenses of Example 19, polymer samples consisting of the coating components are prepared for evaluation. The resulting gels are then hydrated and tested to determine the water content. Solutions are prepared using the two polymer components of a crosslinked coating formed in Example 19: poly (AAm-co-AA) (90/10) and PAE, to have the following composition: 12.55% w / w PAE, 6 , 45% w / w poly (AAm-co-AA) (90/10) and 81% w / w water. The ratio of PAE / poly (AAm-co-AA) (90/10) is identical to that of the IPC salt solution of Example 19, but the individual concentrations of the components are higher to ensure that a gel is formed during autoclaving. The solution is then autoclaved for about 45 minutes at 1210 ° C after which the sample is transformed into a gel. The 165 ΡΕ2461767 gel samples are then prepared for determination of the water content by testing the samples after hydration (n = 3). Hydrated samples are prepared by submerging the gel sample in SoftWear saline for at least about 6 hours (i.e., hydrated overnight).

The hydrated samples are blotted dry and the mass in the hydrated state is recorded through the mass balance. Following mass recording in the hydrated state, the samples are all placed in a vacuum oven labeled at approximately 50øC and dried under Hg vacuum of <1 inch overnight.

The dried samples are removed from the vacuum oven after drying overnight and are then measured to record the dry mass. The water content is calculated using the following ratio:

Water content = (wet mass-dry mass) / wet mass x 100% The water content of the samples is determined to be 84.6 + 0.4% w / w.

This water content of this PAE / poly (AAm-co-AA) hydrogel is believed to represent the hydrogel (crosslinked coating) outer layer of the SiHy contact lenses of Example 19 for the following reasons. It is first reasonably assumed that the lens polymers 166 ΡΕ2461767 of hydrophobic mass (silicone hydrogel) are not present in the outer surface layer. This seems to be a very good starting point based on the XPS data. According to the XPS data in Example 21, there is no or very little silicon content to the surface of the SiHy lens with the crosslinked coating, indicating that the outer surface layer is almost entirely composed of the coating polymers (PAe and PAAm-PAA ). Second, the polyacrylic acid (PAA) coating (transition layer) presumably has a minimal impact on the water content of the surface layer. This principle may not be valid. But, if any charged PAA is present in the surface outer layer, it would still increase the water content beyond 84.6%. Third, a much higher concentration of PAE and PAAm-PAA is required to produce PAE / poly (AAm-co-AA) hydrogel which can produce an artificially reduced result in water content. It is believed that both the presence of PAA in the hydrogel outer layer and the lower crosslink density due to the lower concentration of polymeric materials during crosslinking (in Example 19) may result in a surface layer (hydrogel outer layer) having a water that is even higher than what is measured in the tests in this example. It may be assumed that the outer coating layer of the SiHy contact lenses of Example 19 comprises at least 80% water and may be even higher when fully hydrated. 167 ΡΕ2461767

Example 24

An Abbe refractometer is typically used to measure the refractive index of contact lenses. The difference in refractive index between a test lens and the prism of the instrument creates a single angle of total internal reflectance that results in a visible dark shadow line. The angle at which this line of shadow appears is directly related to the refractive index of the test lens. Most contact lenses (including the uncoated SiHy contact lenses prepared in Example 19) produce a distinct shade line in the Abbe refractometer, but the crosslinked SiH y (i.e. the outer hydrogel layers) of Example 19 does not produce a distinct shade line. This phenomenon is believed to be due to a decrease in the refractive index of the lens at the surface compared to the mass and the fact that the transition from the mass to the surface is not abrupt. It is further believed that near the surface of the lens the water content begins to increase which results in a decrease located at the refractive index of the lens. In effect, this would create simultaneous shadow lines at multiple angles, which would result in a blurred image of the shadow line.

The Abbe data demonstrate that the surface outer layer is characterized by an increase in the water content close to the lens surface consistent with the results described in Example 23. ΡΕ2461767 168

Example 25

The crosslinked SiHy contact lenses (i.e. the hydrogel outer layers) prepared in Example 19, desalted in ultra pure water, are individually placed in a 50 mL disposable beaker with 50 mL ultra pure water and frozen by placing the beaker in a dry ice bath and isopropyl alcohol. The beakers are wrapped in foil and placed on a VirTis Freezemobile 35EL with a vacuum pressure of = 30 pbar and a condenser temperature = -70 ° C. After 24 hours, the aluminum foil is removed to increase heat transfer and the vials are left for another 24-48 hours to remove the residual moisture. The vials are capped to prevent moisture from entering the air until they are analyzed. The lens samples are cut in half and two strips are then cut from the middle of each half and mounted at their ends to image the cuts. Samples are then spray coated with Au / Pd ~ 1 min and exemplified by SEM using a Bruker Quantax Microanalysis System (JEOLJSM-800LV SEM). The sample phase is inclined -0-60 °, as the analyst understands, to achieve the intended orientation of the sample.

It is believed that, when the SiHy contact lenses are lyophilized, the hydrated surface structure of the lenses may be preserved or closed to certain degrees. Figure 4, panel A shows the top view of the SEM image of a surface of a lyophilized SiHy contact lens 169 ΡΕ2461767 prepared in Example 19. It can be seen from Figure 4 that the lyophilized SiHy contact lens has a sponge-like surface structure which would be expected for a hydrogel having a high water content. This result further confirms that the SiHy contact lens of the invention comprises the two hydrogel outer layers of a hydrogel having a high water content. Figure 3, panels B and C, shows the side views at two different angles of a cut of the lyophilized SiHy contact lens shown in panel A. Panels B and C show the thick inner layer with a smooth surface, a transition layer (PAA layer) with a brighter color at the top of the inner layer, and a hydrogel outer layer with sponge-like structures on top of the transition layer. Based on the data presented in panels B and C, the thickness of the lyophilized hydrogel outer layer is calculated to be between about 2 pm and 2.5 pm.

Example 26

PAA-PAA-F polypeptide is synthesized in the home by covalently attaching 5-aminofluorescein to PAAm-PAA (90/10), poly (AAm-co-AA) (90/10) (referred to as PAAm-PAA- by a process similar to that of the PAA-F preparation. Partial sodium salt of poly (AAm-co-AA) (90/10) (-90% solids content, poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from

Polysciences, Inc. and is used as received. The degree of 170 ΡΕ2461767 fluorescein labeling is about 0.04 mole%.

Modified IPC saline solution using PAAm-PAA-F.

This saline solution is prepared by the same procedure as the IPC preparation as described in Example 19, except where PAAm-PAA is replaced by PAAm-PAA-F.

PAA coated lenses The lenses are prepared by casting cast from the lens formulation prepared in Example 19 in a reusable mold (half the female quartz mold and half the male glass mold), similar to the mold shown in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6). The lens formulation in the template is irradiated with UV irradiation (13.0 mW / cm 2) for about 24 seconds. The cast cast contact lenses are drawn and coated by immersing them in the following series of baths: D1 water bath (56 seconds); 6 MEK baths (about 44, 56, 56, 56, 56, and 56 seconds, respectively); Dl water bath (about 56 seconds); a PAA coating solution bath (about 0.36% by weight, acidified with formic acid to about pH 2.0) in 1-PrOH solvent (ca. 44 seconds); a bath of a 50/50 / 50% water / 1-propanol mixture (about 56 seconds); 4 baths of water Dl, each for 56 seconds; a PBS bath for about 56 seconds; separately; and a water bath D1 171 ΡΕ2461767 for about 56 seconds.

Application of reticulated coating

The above prepared PAA-coated lenses are placed in polypropylene lens packaging shells (one lens per shell) with 0.6 mL of the modified IPC salt solution prepared above using PAAm-PAA-F ( half of the saline solution is added before inserting the lens). The blisters are then sealed with metal film and autoclaved for about 30 minutes at about 121øC, forming SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilic polymeric material).

Confocal laser fluorescence microscopy

A piece of a hydrated SiHy lens with crosslinked coating (back prepared) is placed between two glass slides and the image is collected on a laser confocal fluorescence microscope (model # Zeiss LSM 510 Vis). It is swept from the curved front side of the lens to the curved side of the lens base, or vice versa. The presence of PAA-PAA-F is shown by green fluorescence and microscopic images of laser confocal fluorescence can be obtained. Examination of the microscopic images of laser confocal fluorescence reveals that the PAAm-PAA-F rich layer (i.e. the outer layers in hydrogel) is present on both surfaces of the lens 172 ΡΕ2461767 (front and rear surfaces) and the edge while no PAA-PAA-F is observed in the mass matter of the hydrated lens.

Fluorescence intensity profiles are examined by cutting the lens along a line passing through both the anterior and posterior normal surfaces to the posterior surface. The thickness of the PAA-PAA-F rich layer can be calculated from the intensity profile of the fluorescence through the lens. The possible thickness of the outer layer in hydrogel (layer rich in PAAm-PAA-F) is calculated by the distance from zero intensity, after crossing the peak intensity, to zero intensity again. Since there is a possible contribution of unknown factors (such as dispersion) to the fluorescence intensity, the minimum thickness of the layer is the thickness for which a fluorescent intensity of at least 10% of maximum peak intensity is retained. Based on this calculation, the minimum thickness of the PAAm-PAA-F rich layer (hydrated hydrogel outer layer) could be at least about 5 microns.

Example 27

The lenses are fabricated using the D-2 lens formulation (Example 17) to which APMAA monomer was added to a concentration of 1%. LS lenses are prepared by casting from a 173 ΡΕ2461767 lens formulation prepared, as discussed above, in a reusable mold similar to the mold shown in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6). The mold comprises a female mold half made of glass and a quartz male mold half. The UV irradiation source is a Hamamatsu lamp with a cut filter of 380 nm at an intensity of about 4.6 mW / cm 2. The lens formulation in the template is irradiated with UV irradiation for about 30 seconds.

The cast cast lenses are extracted with water-washed, polyacrylic acid (PAA) coated methylethylketone (MEK) by immersing the lenses in a PAA propanol solution (0.0044% by weight, acidified with formic acid to about pH 2 , 5), and hydrated with water. The IPC salt solution is prepared according to the composition described in Example 9 under pre-reaction conditions of 8 h at approximately 60 ° C. The lenses are placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline (half of the IPC saline solution is added before lens insertion). The blister is then sealed with metal foil and autoclaved for about 30 minutes at 121 ° C. The evaluation of the lens surface shows that all test lenses do not exhibit debris adherence. When observed under a darkfield microscope, no cracking lines are visible after the lens is rubbed between the fingers. The lens surface wetting (WBUT) is greater than 10 seconds, lubrication is rated &quot; 1 &quot; and the contact angle is approximately 20Â °.

Example 28 Leak-cast SiHy contact lenses (without any coating) prepared from Example 19 are used. All lenses are extracted in MEK overnight to ensure that all residual monomer is removed. The first group of lenses (lenses with crosslinked and hydrated coating on top) is dipped in a PAA coating solution overnight (0.36% by weight PAA in 1-Propanol, pH 1.7-2.3 adjusted with The lenses after autoclaving are tested (Example 1) and the lenses are added to the lenses and the lenses are added to the lenses of the lenses. in groups of 5) using the gravimetric analysis technique to determine wet and dry contact lens weights (N = 14 for the first contact lens group, N = 18 for the second contact lens group). are shown in Table 8.

Table 8

Wet weight Dry weight Water content (for 5 lenses) (for 5 lenses)% 175 ΡΕ2461767 Mean Stress Mean Stress Stress Mean Stress Stress Stress Group Stress Stress Group Stress Stress Group Stress Stress Stress 0.0947 0.002 30.8 0.4

Statistically there is a significant difference (7 mg) in a wet weight between the first and second groups of contact lenses due to the presence of the hydrated crosslinked coating of the contact lenses compared to the control (uncoated) lenses. However, the difference in dry weight between the first and second contact lens group is about 0.3 mg and is not statistically significant. The water content of the lens for the contact lens can be calculated to be -96% according to the following calculation

It is understood that the water content here calculated for the crosslinked coating on a contact lens may not be accurate because the difference in dry and wet weight between the first and second contact lens groups is too small and even lower than the standard deviation.

Example 29

This Example illustrates how to quantify the lubrication of SiHy contact lenses in accordance with the 176 ΡΕ2461767 inclined plate method (&quot; Derby Friction Test &quot;). The inclined plate method is a simple test to assemble as shown in Figure 5. The assembly for the inclined plate method is comprised of a plastic reservoir or tank 501 which is filled with a phosphate buffered saline (PBS , pH-7.3) 502, a borosilicate glass plate 503 and a shim 506 with an adjustable height between 5 mm and 20 mm. Both the borosilicate glass plate 503 and the shim 506 are submerged in the phosphate buffered saline 502 in the plastic reservoir or tank 501. In one test, a contact lens 504 is placed in the borosilicate glass plate and then in a (τ), where Θ is the critical angle, FN and the normal force, and Ft is the critical angle F, the highest angle at which a lens continues to slide after being pushed, but stops before, or takes more than 10 seconds to, reach the end, is defined as the &quot; critical angle &quot;. The coefficient (CCOF) is the tangent of the critical angle Θ. A lens that does not travel will be below the CCOF, while a lens that does not stop during the distance to travel will be above the CCOF. CCOF are removed from the analysis. The Derby friction test can produce a direct path for measuring the coefficient of kinematic friction.

In the tests according to the slant method 177 ΡΕ2461767, all lenses are stored in a PBS solution at least overnight (&gt; 6 hours) before being tested, to remove any residual packaging solution. The glass plate (borosilicate glass with 6 &quot; x 4 &quot;) is cleaned with a solution of soap (1% Micro-90) and dried (AlphaWipe TX1009). Each plate is carefully rinsed in D1 water, about 2 minutes. A section of the friction plate is tested by rubbing with a finger to ensure that all of the soap solution has been removed. The water is cleaned with paper towels (KimTech Kimwipe # 34705) and inspected in the light to ensure that no foreign particles remain on the glass. The glass plate is placed on shims of various heights in a reservoir or plastic tank and the height of the flat is measured with a micrometer and recorded. The reservoir is filled with phosphate buffered saline (PBS) to ensure that the lens is completely submerged (depth 28 mm).

Each lens is placed on the &quot; starting line &quot; and a 0.79 g (1/4 ") stainless steel ferrule is dropped to produce physiologically relevant pressure) on the surface of the lens. The lens is allowed to slip through the plate and the time taken for the lens to fall to 96 mm is recorded. The lens is moved to the starting position with the weight removed before retesting. This effect of &quot; preloading &quot; should be minimized for better replication. The lens can be tested at multiple angles 178 ΡΕ2461767 to obtain the optimum CCOF.

Sixteen commercial contact lenses and silicone hydrogel contact lenses prepared in Example 19 are tested for CCOF and the results are reported in Table 9. The results show that a SiHy contact lens of the invention (prepared in Example 19 to afford a topcoated coating) has the lowest CCOF between any class of silicone hydrogel lenses that are commercially available and tested and therefore have the highest lubrication.

Table 9

Contact Lenses SiHy CH (mm) CA (2) CCOF Example 19 Y 5, 7 2.2 0.038 DAILIES AquaComfortPlus N 6.0 2.3 0.040 IDay Acuvue N 6.5 2.5 0.043 Dailies Aqua N 6.8 2 , 6 0.045 1-Day Acuvue TruEye (narafilcon B) Y 7.2 2.8 0.048 SofLens Daily Disposable N 7.6 2.9 0.051 1-Day Acuvue Moist N 7, 7 3.0 0.052 Proclear 1-Day N 8 , 3 3.2 0.056 1-Day Acuvue TruEye (narafilcon A) Y 8.8 3.4 0.059 Clariti 1-Day Y 9.2 3.5 0.062 Acuvue Moist Y 7.7 2.9 0.051 Air Optix Aqua Y i -1 V 00 3.1 0.054 179 ΡΕ2461767

Biof inity Y i-1 00 3.1 0.14 PureVision Y 9.4 3.6 0, 063 Acuvue Advance Y 9.7 3.7 0, 065 Acuvue Oasys Y 9.9 3.6.0, 066 Clariti Y 12.5 4.8 0, 084 CH: Critical height; C.A .: Critical angle

Example 30

This Example illustrates how to characterize the negatively charged surface of a SiHy contact lens according to the Positively Charged Adhesion Test. The surface charge of a lens surface can be detected indirectly through its interaction with charged particles or beads. A negatively charged surface will attract positively charged particles. A negative charge or substantially negative charge surface will not attract positively charged particles or will attract a few positively charged particles.

Uncoated SiHy contact lenses (i.e. leak-cast and MEK-extracted as described in Example 19), PAA-coated SiHy contact lenses (as prepared in Example 19), and SiHy contact lenses with a coating (as prepared in Examples 14 and 19) are 180 ΡΕ2461767 tested as follows. The PAA coating of the PAA coated contact lenses has a surface carboxylic group concentration of about 62.5% by weight (mCOOH / maa in which McoOH is the mass of the carboxylic acid group and Maa is the mass of acrylic). The crosslinked coating of the contact lenses of Example 14 is theoretically free of carboxylic acid groups, whereas the crosslinked coating of the contact lenses of Example 19 may contain a reduced surface concentration of carboxylic acid groups (should ---. The lens is immersed in a dispersion with positively charged particles after appropriate rinsing, the number of particles adhered to the lens being visualized and calculated or counted.

DOWEX ™ 20x4 mesh DOWEX ™ resins are purchased from Sigma-Aldrich and used as received. DOWEX ™ 20x4 mesh DOWEX ™ resins are spherical, Type I strong base anion resins and are styrene / divinylbenzene copolymer containing N + (CH 3) 3 Cl "functional groups and 4% divinylbenzene functional groups. About 5% of 1x4 mesh 20-50 resins are dispersed in PBS and are well mixed by shaking or swirling at approximately 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and subjected to vortexing between 1000-1100 rpm for 1 min, followed by washing with D1 water and swirling 181 ΡΕ2461767 for 1 min. The lenses are then placed in water in Petri dishes in glass and images of the lenses are taken with a Nikon optical microscope, using backlight. As shown in Figure 6, nearly the entire surface of the PAA coated lenses is covered with positively charged adhered particles (Figure 6a), while a total of about 50 positively charged particles are adhered to lenses with crosslinked coating prepared in Example 19 (Figure 6B) and no positively charged particles are adhered to lenses with the crosslinked coating prepared in Example 14 (Figure 6C). Some lightly adhered particles may fall off the surface of the lens and may also be found in the water surrounding the lens.

It will be understood that, when larger positively charged particles (i.e., DOWEX ™ monosphere ion exchange resins, crosslinked polystyrene beads, chloride form, -590 microns in size, from Sigma-Aldrich) are used in the tests, the number of particles adhered on the particles may be smaller. About 30% of these DOWEX monosphere resins are dispersed in PBS. The lenses are immersed in this dispersion for ~ 1 min, followed by washing with water D1. The lenses are then placed in water in glass petri dishes and images of the lenses are taken with a Nikon optical microscope using backlight. It has been found that there are many particles (crca of 200 particles) adhered to PAA-coated lenses and no particles are adhered to the cross-linked lenses 182 ΡΕ2461767. Some commercially available contact lenses are also tested. No particles were observed on the following lenses: Acuvue® Advance®, Acuvue® Oasys®, Avaira ™, Biofinity®, Air Optic® TruEye ™, and Focus® Night &amp; Day®. Particles are observed on the following 4 lens types (in the order of greatest number of particles): PureVision®, 1 Day Acuvue® Moist®, Proclear 1 day, Acuvue® lens (Etafilcon A). Almost the entire surface of the Acuvue® lens (Etafilcon A) is covered with positively charged adhered particles.

Negatively charged resins (Amberlite CG50) are purchased from Sigma and used as received. About 5% of these Amberlite CG50 beads are dispersed in PBS and vortexed at about 1000 rpm for 10 seconds. The PAA coated lenses are immersed in this dispersion and swirled between 1000-1100 rpm for 1 min, followed by washing with DI water and vortexed for 1 min. The lenses are then placed in water in a glass petri dish and images of the lenses are taken with Nikon optical microscope using backlight. No Amberlite particles (negatively charged) were found on the PAA coated lenses.

In this experiment, negatively charged beads (Amberlite CG50), which are coated with polyethyleneimine (PEI, a positively charged electrolyte) are used. The PEI coating process is carried out as follows. PEI (Lupasol SK, 24% in water, Mw of 183 ΡΕ2461767 -2000000) is purchased from BASF and used as received. Prepare an aqueous dispersion of 1% Amberlite particles and 5% PEI. Adjust the pH to 7 and make sure the solution is thoroughly mixed (for example, stirring for 30 minutes). The dispersion is then suspended in a large amount of water 2 to 3 times and filtered 2 to 3 times before collecting the particles (Amberlite coated with PEI). About 5% of PEI-coated Amberlite CG50 particles are dispersed in PBS and vortexed at about 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and swirled between 1000-1100 rpm for 1 min, followed by washing with D1 water and swirling for 1 min. The lenses are then placed in water in Petri dishes in glass and images of the lenses are taken with Nikon optical microscope, using backlight. It is noted that there are many PEI-coated Amberlite particles (positively charged particles due to the presence of PEI) adhered to the PAA coated lenses (Example 19). However, there are virtually no PEI-coated Amberlite particles adhered to the uncoated SiHy contact lenses (Example 19), the cross-coated SiHy contact lenses (Example 19), or the PAExPAA coated lenses (Example 184 ΡΕ2461767

Example 31

Preparation of samples

AFM studies on SiHy contact lenses (prepared in Example 19) were conducted in the hydrated state and in the dry state. A lens is removed from its blister pack (sealed and autoclaved) and a cut is made (for example, using a razor blade). The cut-off piece of the lens is vertically mounted on a metal clip, as shown in Figure 7. A small piece of lens protrudes from the top of the holder to allow scanning by the AFM tip (above the cut of the lens in Figure 7).

Experience with AFM

Two separate AFM instruments are used to characterize lens cuts. In both cases (except for dried samples), the AFM scan is performed under phosphate buffered saline (PBS with or without NaCl but having substantially the same osmolarity as physiological saline) to maintain the fully hydrated state of the sample in hydrogel. The first AFM instrument is Veeco BioScope AFM with a Nanoscope IV controller. The data are collected using triangular silicon arms with a constant spring of 0.58 N / m and a nominal radius 185 ΡΕ2461767 of curvature of 20-60 nm. The sweeps are performed in constant contact (force-volume) mode with a probe velocity of 30 microns / second and a force-volume sweep speed of 0.19 Hz. Topographic data and force-volume data are collected simultaneously. Each force curve consisted of about 30 data points. The lens is completely immersed in PBS during the AFM scan. Typically, a scan size of at most 20 microns is used to achieve a sufficiently high resolution for the force-volume image. Force marks of 128x128 pixels are collected in about 3 hours per images.

An AFM image of a cut of a crosslinked SiHy contact lens (Example 19) in a fully hydrated state is obtained by the Force-Volume method and is shown in Figure 8. In the image, the darker color region 420 indicates the coating and the lighter color region 410 indicates the mass matter of the lens. The average thickness of the crosslinked coating (i.e. the outer, anterior and posterior layers) of the SiHy contact lens (Example 19) is determined to be about 5.9 Âμm (deviation 0.8 Âμm) as obtained from 7 images, 4 lenses. The AFM technique allows the determination of the surface modulus (surface smoothness) at specific locations on the lens cut. Figure 9 shows a cross-sectional surface profile profile of a contact lens having a crosslinked coating (prepared in Example 19) in a fully hydrated state. Because the surface modulus of a material is proportional to the deflection of the arm, a cut-off surface modulus profile of a contact lens can be roughly obtained by marking the values of the arm deflection (as a measure for the surface modulus of a material at a specific location in the lens cut) as a function of the distance from the side (front or back surface) of the cut along two lines through the cut shown in Figure 8. As shown in Figure 9, the crosslinked coating the anterior and posterior exterior surfaces of the contact lens of Example 19) is softer than the mass (inner layer) of the silicone hydrogel lens material. By moving along two lines, the surface modulus first remains almost constant with a mean arm deflection of about 52 nm (i.e., average surface modulus) over the area between 0 and about 5 , 9 microns, and then gradually increases in the innermost locations of the lens until they reach a maximum and remain approximately constant therefrom (plateau) with a mean arm deflection of about 91 (i.e., mean surface modulus) over the area above about 7 microns. The transition from the softer crosslinked coating to the harder SiHy material, which occurs gradually over the range of a few microns, suggests that a gradient in the morphology or composition (water content) may be present between the surface of the coating and the mass of the coating. lens. The surface modules in the region between 5.9 187 ΡΕ2461767 microns and about 7 microns, i.e., a region around the boundary between the hydrogel outer layer and the inner layer of the silicone hydrogel material, are not used in the calculation of the average surface modulus. The hydrogel (reticulated coating) outer layers of the SiHy contact lens (Example 19) may be calculated to have a reduced surface modulus

* sm, -smZI f -x 1QQ% _ SM. in which is the mean surface modulus of the back or anterior layer in hydrogel and Sfs> sr is the average surface modulus of the inner layer) of about 43%.

SiHy contact lenses (prepared in Example 19) are studied with the second AFM instrument. Scanning is performed using a Bruker Icon AFM in Quantitative Nanomechanical Measurements (QNM Peak Force) mode using lenses either in the fully hydrated state (PBS without NaCl but with glycerol to achieve similar osmolality) or in the dry state. The lens cutout is mounted on a metal clip as described above. Test conditions include a Spring Constant of 1.3 N / m, Tip Radius of 33.3 nm, Sensitivity of 31 nmN, Scanning Speed of 0.4 Hz and a Scan Resolution of 512 × 512. The AFM image of a cut of the SiHy contact lens (Example 19) in the fully hydrated and dry state is obtained according to the QNM Peak Force method. By analyzing the obtained images, the thickness of the ΡΕ2461767 crosslinked coating in the fully hydrated state is determined to be about 4.4 microns, while the thickness of the crosslinked coating in the dry state is determined to be about 1.2 microns for dry sample by vacuum, about 1.6 microns for oven dried sample. The ratio of volume increase per water in which Lwet is the average thickness of the hydrogel outer layer of the SiHy contact lens in a fully hydrated state, and LDry is the average thickness of that outer layer in the hydrogel of the SiHy contact lens in the dry state) of the crosslinked coating of the SiHy contact lens (prepared in Example 19) is calculated to be about 277% (oven dried sample) or about 369% vacuum).

Example 32

Preparation of Lens Formulations Formulation I is prepared by dissolving the components in 1-propanol to have the following composition: 33% by weight of EC-PDMS macromer prepared in Example 2, 17% by weight N- [tris (trimethylsiloxy) - silylpropyl] acrylamide (TRIS-Am), 24% by weight of N, N-dimethylacrylamide (DMA), 0.5% by weight of N- (carbonyl-methoxypolyethylene glycol-2000) 1,2-distearyl sn-glycero -3-phosphoethanolamine, sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of visitint (5% blue pigment dispersion of 189 ΡΕ2461767 phthalocyanine of copper in tris (trimethylsiloxy) silylpropyl methacrylate, TRIS), and 24.5% by weight of 1-propanol. Formulation II is prepared by dissolving the components in 1-propanol to have the following composition: 32% by weight of EC-PDMS macromer prepared in Example 2, about 21% by weight TRIS-Am, about 23% by weight of DMA, 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of visitint (5% of copper phthalocyanine blue pigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppm H-time and about 22% by weight of 1-propanol.

Lens Preparation

The lenses are prepared by casting from a back lens formulation prepared in a reusable mold (quartz female half and male half glass mold), similar to the mold shown in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6). The UV irradiation source is a Hamamatsu lamp with a cut filter WG335 + TM297 at an intensity of about 4 mW / cm2. The lens formulation in the template is irradiated with UV irradiation for about 25 seconds. Cast cast lenses are extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol).

Application of PAA Primer on SiHy Contact Lenses 190 ΡΕ2461767

A polyacrylic acid (PAA-1) coating solution is prepared by dissolving an amount of PAA (MW: 450kDa, from Lubrizol) in a given volume of 1-propanol to have a concentration of about 0.36% by weight and the pH is adjusted with formic acid to about 2.0.

Another PAA coating solution (PAA-2) is prepared by dissolving a quantity of PAA (MW: 450kDa, from Lubrizol) in a given volume of an organic solvent (50/50 of 1-propanol / H2 O) to have a concentration of about 0.39% by weight and the pH is adjusted with formic acid to about 2.0.

The obtained SiHy contact lenses are subjected to one of the diving processes shown in Tables 10 and 11.

Table 10

Baths Time Dive Procedure 20-0 20-1 20-2 20-3 20-4 20-5 1 56s H20 H20 H20 H20 H20 H20 2 44s MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK MEK 4 56s MEK MEK MEK MEK MEK MEK MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK Mek MEK MEK MEK PAA-2 PAA-2 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA- 56s H20 H20 H20 H20 H20 H20 14 56s H20 H20 H20 H20 H20 H20 15 56s PBS PBS PBS PBS PBS PBS 16 56s H20 H20 H20 H20 H20 H20 H20 PrOH represents 100% 1-propanol; phosphate buffered saline; MEK ketone; 50/50 means a 50/50 blend. PBS stands for methylethyl-solvent means 1-PrOH / H2O

Table 11

Baths Time Dive Procedure 80-0 80-1 80-2 80-3 80-4 80-5 80-6 1 56s H20 H20 H20 H20 H20 H20 H20 2 44s MEK MEK MEK MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK 4 56s MEK MEK MEK MEK MEK MEK MEK MEK 56 MEK MEK MEK MEK MEK 56 MEK MEK MEK MEK MEK 56 MEK MEK MEK MEK MEK MEK MEK MEK MEK MEK MEK 56 56 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 10 56s PAA-1 50/50 PrOH 50/50 PrOH PrOH H20 192 ΡΕ2461767 11 56s H20 H20 H20 50/50 PrOH 50/50 50/50 12 44s H20 H20 H20 H20 H20 H20 H20 13 56s H20 H20 H20 H20 H20 H20 H20 14 56s H20 H20 H20 H20 H20 H20 H20 15 56s PBS PBS PBS PBS PBS PBS PBS 16 56s H20 H20 H2O H2 O H2 O H2 O H2 O 100% 1-propanol; PBS stands for phosphate buffered saline; MEK stands for methylethylketone; 50/50 means a solvent mixture 1-PrOH / H 2 O at 50/50 φ

Application of Reticulated Hydrophilic Coating

Partial sodium salt of poly (acrylamidoacrylic acid), Poly (AAm-co-AA) (90/10) (-90% solid content, poly (AAm-co-AA) 90/10), Mw 200,000) is purchased from Polysciences, Inc. and is used as received. (PAE) (Kymene, an azetidinium content of 0.46, NMR) is purchased from Ashland as an aqueous solution and is used as received. In-pack crosslinking (IPC) salt solution is prepared by dissolving about 0.07% w / w Poly (AAm-co-AA) (90/10) and about 0.15% PAE (an equivalent initial millimolar azetidinium content of about 8.8 millimoles) in phosphate buffered saline (PBS) (about 0.044% w / w NaH 2 PO 4 .H 2 O, about 388% w / w Na 2 HPO 4 .2H 2 O, about 0.79 w / w% NaCl) and adjusting the pH to 7.2-7.4. Then, the IPC salt solution is pretreated thermally for about 4 hours to about 70 ° (pre-heat treatment). During this heat pretreatment, the poly (AAm-co-AA) and PAE are partially crosslinked 193 ΡΕ2461767 (i.e., not consuming all the azetidinium groups of the PAE) to form a thermally cross-linkable hydrophilic polymer material water containing azetidinium groups within the branched polymer network in the IPC salt solution. After the heat pretreatment, the IPC salt solution is filtered using a 0.22 micron polyether sulfone [PES] membrane filter and is cooled again to room temperature. 10 ppm of hydrogen peroxide are then added to the final IPC saline to prevent the development of bioburden and the IPC saline solution is filtered using 0.22 micron polyether sulfone [PES] membrane filter.

The above lenses prepared with a PAA primer coating overlay are placed in polypropylene lens packaging shells (a lens shell) with 0.6 mL of the IPC saline solution (half of the saline is added before inserting the lens ). The blisters are then sealed with metal foil and autoclaved for about 30 minutes at about 121øC, forming SiHy contact lenses with crosslinked hydrophilic coatings on top.

Characterization of SiHy lenses

The resulting SiHy contact lenses with crosslinked hydrophilic coatings having a central thickness of about 0.95 microns have an oxygen permeability (Dkc or calculated Dk intrinsic) of about 142 to about 150 barrers, an elastic modulus from about 0.72 to about 0.79 MPa, a water content of about 30% to about 33% by weight, a relative ionic permeability of about 6 (relative to Alsacon lenses), and a contact angle of from about 34 to about 47 degrees.

Characterization of the Nano-textured Surfaces of the Contact Lens Transmission-Differential-Interference-Contrast Method (TDIC). Contact lenses are placed and examined focusing through the lens using a Nikon ME600 microscope with contrast transmission differential contrast optics using a 40x objective lens. The TDIC images obtained are then evaluated to determine the presence of wrinkled surface patterns (for example, random or ordered caterpillar-like patterns, or the like). Reflection-Differential-Interference-Contrast Method (RDIC). The lenses are placed on a glass slide and flattened to make 4 radial cuts at all -90 degrees. Excess saline solution is blown off the surface using compressed air. The surface of the lenses is then examined using Nikon Optiphot-2 with contrast reflection differential contrast optics for the presence of wrinkled surface patterns on the surfaces 195 ΡΕ2461767 of a contact lens using lx, 20x and 50x objective lenses. A representative image is acquired from each side using 50x objective lenses. The contact lens is then turned upside down, excess saline is removed and the other side of the contact lens is inspected in the same manner. The obtained RDIC images are then evaluated to determine the presence of wrinkled surface patterns (for example, caterpillar, random and / or ordered patterns, or the like).

Microscopy with Dark Field Light (DFLM).

Generally, the DFLM is based on dark field lighting which is a method of enhancing the contrast in the observed samples. This technique consists of an external or blocked lux source of the field of view of the observer to illuminate a sample at an angle relative to the transmitted normal light. Since the non-scattered light from the source is not picked up by the lens, it is not part of the image and the background of the image appears dark. As the light source is illuminating the sample at an angle, the light observed in the sample image is that which is scattered by it towards the oscillator. Then, contrast is created between this scattered light from the sample and the dark background of the image. This contrast mechanism makes dark illumination especially useful for observing scattered phenomena such as haze. The DFLM is used to assess the fogging of the 196 ΡΕ2461767 contact lenses, as follows. It is believed that because the dark field installation involves scattered light, dark field data could produce the worst case of haze calculation. In 8-bit gray scale images, a gray scale intensity value (GSI Gray scale intensity) is assigned to each image pixel in the range of 0-255. Zero represents a pixel that is perfectly black and 255 represents a pixel that is perfectly white. An increase in scattered light captured in the image will produce pixels with higher GSI values. This GSI value can then be used as a mechanism to quantify the amount of scattered light observed in the dark field image. The haze is expressed by averaging the GSI values of all pixels in an area of interest (AOI) (for example, a complete lens or the lenticular zone or optical zone of a lens). The experimental setup consists of a microscope or equivalent optics, a digital camera attached thereto, and a dark field holder with ring light and variable intensity light source. The optics are drawn / arranged so that the entire contact lens to be observed fills the field of view (typically ~ 15mm x 20mm field of view). Illumination is marked to an appropriate level to observe the desired changes in the relevant samples. The light intensity is adjusted / calibrated to the same level for each set of samples using a light density / dispersion pattern as is known to those skilled in the art. For example, a pattern consists of two overlapping plastic lamellae (identical and slightly or moderately frosted). 197 ΡΕ2461767

This pattern consists of areas with three GSI of different averages that include two areas with intermediate gray scale and saturated white (edge) levels. The black areas represent the empty dark field. Black and saturated white areas can be used to check the gain and to divert (contrast and brightness) the camera markings. Intermediate gray levels can produce three dots to verify the linear response of the camera. The light intensity is adjusted so that the average GSI of the empty darkfield approaches 0 and that of a defined AOI in a digital image of the pattern is always equal within + 5 GSI units. After calibration of the light intensity, a contact lens is immersed in phosphate buffered saline at 0.2 æm in a quartz Petri dish, or on a plate or with similar clarity, which is placed on the DFLM support. A digital image of the 8-bit gray scale lens is then acquired as viewed using calibrated illumination and the average GSI of an AOI defined within the portion of the image containing the lens is determined. This is repeated for a set of contact lens samples. Calibration of light intensity is periodically re-evaluated during a test to ensure consistency. The level of fog in a DFLM examination refers to a fogging

of DFLM

SiHy contact lenses, whose PAA primer coating is obtained according to any of the 198-2041767 diving procedures, are determined to have an average DFLM mist of about 73% and show wrinkled surface patterns (random caterpillar patterns) that can be visually observed upon examination of the hydrated state contact lens according to the RDIC or TDIC method as described above. However, wrinkled surface patterns have practically no adverse effects on the transmissibility of light from contact lenses.

SiHy contact lenses, whose primary PAA coating is obtained according to any of the dip processes 20-1 and 20-4, are determined to have a reduced average mist DFLM of about 26% Probably due to the presence of particles of pigment visitint) and exhibit no noticeable patterns of wrinkled surface (caterpillar random patterns) when examined for RDIC or TDIC as described above.

A high percentage of SiHy contact lenses, whose primary PAA coating is obtained according to the dip process 20-5, are determined to have moderate to moderate DFLM haze of about 45% and show slightly notable wrinkled surface patterns when both RDIC and TDIC as described above. However, wrinkled surface patterns have practically no adverse effects on the transmissibility of light from contact lenses. 199 ΡΕ2461767

SiHy contact lenses, whose PAA primer coating is obtained in accordance with any of the 80-1, 80-2, 80-5, 80-6 and 80-6 bond processes, exhibit no noticeable patterns of wrinkled surface when examined in RDIC or TDIC as described above. However, SiHy contact lenses, whose primary PAA coating is obtained in accordance with any of the dipping processes 80-0 and 80-4, exhibit remarkable patterns of wrinkled surface when examined in RDIC or TDIC as described above. But wrinkled surface patterns have practically no adverse effects on the transmissibility of light from contact lenses.

Example 33

Synthesis of branched amphiphilic UV absorbent copolymer

A 1-L jacketed reactor is equipped with a 500 mL addition funnel, head stirring, reflux condenser with nitrogen valve / vacuum inlet thermometer adapter and sampling adapter. 89.95 g of 80% of the ethylenically partially functionalized polysiloxane prepared in Example 17, A is charged into the reactor and then degassed under vacuum at less than 1 mbar at room temperature for about 30 minutes. The monomer solution prepared by mixing 1.03 g of HEMA, 50.73 g of DMA, 2.76 g of Norbloc methacrylate, 52.07 g of TRIS and 526.05 g of ethyl acetate is charged into the addition funnel 200 ΡΕ2461767 followed by a vacuum degassing of 100 mbar at room temperature for 10 minutes and then refilled with nitrogen gas. The monomer solution is degassed under the same conditions for a further two cycles. The reactor is then charged with the monomer solution. The reaction mixture is heated to 67 ° C with suitable stirring. While heating, a solution composed of 2.96 g of mercaptoethanol (chain transfer agent, CTA) and 0.72 g of dimethyl 2,2'-azobis (2-methylpropionate) (V-601-initiator) and 76 , 90 g of ethyl acetate is charged into the addition funnel followed by the same degassing process as the monomer solution. When the reactor temperature reaches 67øC, the initiator / CTA solution is also added to the reactor. The reaction is run at 67 ° C for 8 hours. After the copolymerization is complete, the temperature of the reactor is cooled to room temperature.

Synthesis of UV absorbent amphiphilic branched prepolymer with 100 The above prepared copolymer solution is ethylenically functionalized to form an amphiphilic branched prepolymer by the addition of 8.44 g of EMI (or 2-isocyanatoethylmethacrylate in a desired amount of molar equivalent) in the presence of 0 , 50 g DBTDL. The mixture is stirred at room temperature under a sealed condition for 24 hours. The prepared prepolymer is then stabilized with 100 ppm of hydroxy tetramethylene 201 ΡΕ2461767 piperonyloxy before the solution is concentrated to 200 g (-50%) and filtered through filter paper having a pore size of 1 μm. After the reaction solvent is exchanged for 1-propanol through repeated cycles of evaporation and dilution, the solution is ready to be used for formulation. The solids content is measured by removal of the solvent in a vacuum oven at 80 ° C.

Preparation of the lens formulation

A lens formulation is prepared to have the following composition: 71 wt% prepolymer prepared above; 4 wt% DMA; 1% by weight TPO; 1 wt% DMPC; 1% by weight of Brij 52 (from Sigma-Aldrich), and 22% by weight of 1-PrOH.

Lens preparation

The lenses are fabricated by cast molding the lens formulation back prepared using a reusable mold, similar to the die cast in Figs. 1-6 in U.S. Patent Nos. 7,384,590 and 7,387,759 (Figs 1-6) under the spatial limitation of UV irradiation. The mold comprises a female mold half made of glass and a male mold half made of quartz. The UV irradiation source is a Hamamatsu lamp with the cut filter 380 nm at an intensity of about 4.6 mW / cm 2. The lens formulation in the template is irradiated with UV irradiation for about 30 seconds. 202 ΡΕ2461767 344 The cast cast lenses are extracted with water-washed, polyacrylic acid (PAA) coated methylethylketone (MEK), by immersing the lenses in a PAA propanol solution (0.004% by weight, acidified with formic acid to about pH 2.0) and hydrated in water. The IPC salt solution is prepared from a composition containing about 0.07% PAAm-PAA and PAE sufficient to yield an initial azetidinium content of approximately 8.8 millimoles equivalents / Liter (-0.15% of PAE) under pre-reaction conditions of 6 hours at approximately 60 ° C. 5 ppm of hydrogen peroxide is then added to the IPC salt solution to prevent the development of bioburden and the IPC salt solutions are filtered using a 0.22 micron polyether sulfone [PES] membrane filter. The lenses are placed in a polypropylene lens packaging shell with 0.6 mL of IPC saline solution (half of the saline solution is added before lens insertion). The blister is then sealed with metal foil and autoclaved for 30 min at 121 ° C.

Lens Characterization

The obtained lenses have the following properties: E '~ 0.82 MPa; DKC ~ 159.4 (using lotrafilcon B as reference lenses, a mean central thickness of 80 Âμm and an intrinsic Dk 110); PI-2,3; % water -26.9; and% UVA / UVB T-4.6 / 0.1. When observed under the field microscope 203 ΡΕ2461767 action is dark, no fissu lines are visible: after rubbing the test lenses. The lenses &lt; very lubricated in a digital friction test and equivalent to the control lenses.

Lisbon, August 8, 2013

Claims (15)

A silicone hydrogel contact lens, comprising: an anterior surface and a posterior rear surface; and a layered structural configuration from the front surface to the back surface, wherein the layered structural configuration includes a front hydrogel outer layer, an inner layer of a silicone hydrogel material and a hydrogel rear outer layer, wherein the The silicone hydrogel material has an oxygen permeability of at least about 50 barrers, and a first water content of from about 10% to about 70%, wherein the hydrogel front and back outer layers have a substantially uniform thickness and fuse at the peripheral edge of the contact lens to completely enclose the inner layer of the silicone hydrogel material, wherein the hydrogel outer and rear outer layers independent of each other have a second water content greater than WCsiHy, such as characterized by either (a) having a water-swelling ratio of at least about 100% if WCsiHy &lt; 45% either (b) for having a ratio of volume increase per 120 water WC of at least about 1 wt% if WCsiHy &lt; 45%, where the thickness of each of the anterior and posterior hydrogel outer layers is from about 0.1 Âμm to about 20 Âμm, as measured with atomic force microscopy through a cut from the posterior surface to the anterior surface of the silicone hydrogel contact lens at completely hydrated state. The silicone hydrogel hydrated contact lens of claim 1, wherein the silicone hydrogel material has an oxygen permeability of at least about 60, preferably at least 70, more preferably at least 90, most preferably at least about 110 barrers. The hydrogel hydrated contact lens of claim 1 or 2, wherein the silicone hydrogel material has a first water content WCSiHy is from about 10% to about 65%, preferably from about 10% to about 10% by weight. about 60%, more preferably from about 15% to about 55%, most preferably from about 15% to about 50%. 3 ΡΕ2461767 The silicone hydrogel hydrated contact lens of any one of claims 1 or 3, wherein the hydrogel anterior and posterior exterior layers independently of each other have a second water content greater than WCsiHy, as is either (a) having a water-swelling ratio of at least about 150%, preferably at least about 200%, more preferably at least about 250%, most preferably at least about 300%) if WCSiHy , &lt; 45% either (b) having a water-swell ratio of at least about 140% WC SiHv ·%, Si% Preferably SiO2, preferably SiO2, SiO2, SiO2, SiO2, SiO2, SiO2 and SiO2. 45! The silicone hydrogel hydrated contact lens of any of claims 1 to 4, wherein the thickness of each of the outer anterior and posterior hydrogel layers is from about 0.25 μιη to about 15 μιη, preferably from about from 0.5 μπα to about 15 μιη, more preferably from about 1 μιη to about 10 μπι, as measured by atomic force microscopy through a cut from the posterior surface to the anterior surface of the hydrogel contact lens of silicone in a fully hydrated state. The silicone hydrogel contact lens of any of claims 1 to 5, wherein the hydrogel anterior and posterior outer layers independently of one another have a water-swelling ratio of at least about 150% if at least about 200% if WCSiHy &lt; 55%, or at least about 200% if WCSiHy <60%, or at least about 250% if WCsiHy &lt; 65%, or at least about 300%. The hydrogel silicone hydride contact lens of any of claims 1 to 6, wherein the silicone hydrogel material has an oxygen permeability of at least about 79, and a first water content of from about 15% to about 55% by weight, wherein the thickness of each of the outer anterior and posterior hydrogel layers is from about 0.25 μιη to about 15 μm. The silicone hydrogel hydride contact lens of any of claims 1 to 7, wherein the hydrogel outer and rear outer layers independent of each other have a reduced surface modulus of at least about 20%, preferably at least about preferably at least about 30%, more preferably at least about 30%, still more preferably at least about 35%, most preferably at least about 40% relative to the inner layer. The silicone hydrogel hydride contact lens of any one of claims 1 to 8, wherein the silicone hydrogel material has an elastic modulus 5 ΡΕ2461767 from about 0.4 MPa to about 1.5 MPa. The hydrogel hydrated contact lens of any of claims 1 to 9, wherein the silicone hydrogel contact lens further comprises, in its layered structural configuration, two transition layers of polymeric matter (s), wherein each of the transition layers is located between the inner layer and one of the hydrogel anterior and posterior outer layers and has a substantially uniform thickness, wherein the thickness of each transition layer is at least about 0.05 μm, preferably from about 0.05 Âμm to about 10 Âμm, more preferably from about 0.1 Âμm to about 7.5 Âμm, still more preferably from about 0.15 Âμm to about 5 Âμm. The hydrogel hydrated contact lens of any of claims 1 to 10, wherein the silicone hydrogel contact lens has a surface lubrication characterized by a critical coefficient of friction of about 0.043 or less, preferably about 0.040 or less, a surface hydrophilicity characterized by a water break time of at least 10 seconds; a surface wetting characterized by an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, still more preferably about 60 degrees or less, most preferably about 50 degrees or less; 6 ΡΕ2461767 or combinations thereof. The silicone hydrogel hydride contact lens of claim 10, wherein the transition layers comprise a carboxyl polymer containing (COOH). The hydrogel hydrated contact lens of any of claims 1 to 12, wherein the hydrogel front and back outer layers are formed by the application and cross-linking of a water-soluble crosslinkable hydrophilic polymeric material onto a pre-contact lens shaped silicone hydrogel, wherein the silicone hydrogel preformed contact lens comprises amino and / or carboxyl groups on and / or near the contact lumen surface or a base coat comprising amino and / or carboxyl groups; wherein the preformed silicone hydrogel contact lens becomes the inner layer after cross-linking, and wherein the water-crosslinkable, hydrophilic polymeric material is a partially cross-linked polymeric material comprising a three-dimensional network and crosslinkable groups, preferably azetidinium groups within the network. The silicone hydrogel hydrated contact lens of claim 13, wherein the water-soluble crosslinkable hydrophilic polymeric material comprises (i) from about 20% to about 95% by weight of first polymer chains derived from a polyamine or 7 ΡΕ2461767 epichlorohydrin functionalized polyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilic enhancer agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group and combinations thereof, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent bonds, each formed between a azetidinyl group of the polyamine or polyamidoamine functionalized by epichlorohydrin and an amino, carboxyl or thiol group of the hydrophilic enhancing agent and (iii) azetidinium groups which are parts of the first polymer chains or pendent or terminal groups covalently attached to the first polymer chains and wherein the hydrophilic polymer as the hydrophilic enhancing agent is: PEG-NH 2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multi-arms PEG with one or more amino, carboxyl or thiol groups; dendrimers of PEG with one or more amino, carboxyl or thiol groups; a diamino, dicarboxyl, monoamino or monocarboxyl terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer; a copolymer which is a product of the polymerization of a composition comprising (1) about 60% by weight or less, preferably from about 0.1% to about 30%, more preferably from about 0.5% to about 20%, still more preferably from about 1% to about 15% by ΡΕ2461767 weight of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinylic monomer; or combinations thereof, wherein PEG is a polyethylene glycol segment, wherein the reactive vinyl monomer is selected from the group consisting of amino-C 1 -C 6 alkyl (meth) acrylate, C 1 -C 6 alkylamino-C 1 -C 6 alkyl (meth) acrylamide, allylamine, vinylamine, amino-C 1 -C 6 alkyl (meth) acrylamide, C 1 -C 6 alkylamino-C 1 -C 6 alkyl (meth) acrylamide, acrylic acid, alkylacrylic acid, N, N-2-acrylamidoglycolic acid, -acrylic acid, alpha-phenyl acrylic acid, beta-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid , maleic acid, fumaric acid, tricarboxyethylene, and combinations thereof, wherein the non-reactive vinyl monomer is selected from the group consisting of acrylamide, methacrylamide, N, N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N, N-dimethylaminoethyl methacrylate , N-dimethylaminopropylmethacrylamide, N, N-dimethylaminopropylacrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N- [tris (hydroxymethyl) methyl] acrylamide, N 3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, a vinyl monomer containing phosphoryleolin, ( methoxy) -acrylate copolymer having a weight-average molecular weight of up to 1500 Daltons, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, alcohol allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer) and combinations thereof. The hydrogel hydrated contact lens of any of claims 1 to 14, wherein the silicone hydrogel material is obtained from a silicone hydrogel lens formulation comprising at least one component selected from the group consisting of a silicone-containing vinyl monomer, a silicone-containing vinyl macromer, a silicone-containing prepolymer, a hydrophilic vinyl monomer, a hydrophobic vinyl monomer, a crosslinking agent, a free radical initiator, a hydrophilic vinylic macromer / prepolymer and a combination thereof . Lisbon, August 8, 2013